Hydroxyl-platelet-activating factor exists in blood of healthy volunteers and periodontal patients.

Periodontal diseases are localized chronic inflammatory conditions of the gingival and underlying bone and connective tissue. Platelet-activating factor (PAF), a potent inflammatory phospholipid mediator that has been previously detected in elevated levels in inflamed gingival tissues, in gingival crevicular fluid and in saliva, is implicated in periodontal disease. Our results from previous studies showed that the biologically active phospholipid detected in gingival crevicular fluid is a hydroxyl-PAF analogue. In this study, hydroxyl-PAF analogue was detected for the first time in human blood derived from patients with chronic periodontitis as well as from periodontally healthy volunteers. The hydroxyl-PAF analogue was purified by high-performance liquid chromatography, detected by biological assays and identified by electrospray analysis. In addition, the quantitative determination of PAF and hydroxyl-PAF analogue (expressed as PAF-like activity) showed a statistically significant increase in the ratio of hydroxyl-PAF analogue levels to PAF levels in periodontal patients, suggesting that this bioactive lipid may play a role in oral inflammation

Beneficial anti‐platelet and anti‐inflammatory properties of irish apple juice and cider bioactives

peer-reviewedSeveral bioactives from fruit juices and beverages like phenolics, nucleotides and polar lipids (PL) have exhibited anti‐platelet cardio‐protective properties. However, apple juice and cider lipid bioactives have not been evaluated so far. The aim of this study was to investigate the an‐ ti‐platelet and anti‐inflammatory effects and structure activity relationships of Irish apple juice and Real Irish cider lipid bioactives against the platelet‐activating factor (PAF)‐ and adenosine di‐ phosphate (ADP)‐related thrombotic and inflammatory manifestations in human platelets. Total Lipids (TL) were extracted from low, moderate and high in tannins apple juices and from their de‐ rived‐through‐fermentation cider products, as well as from commercial apple juice and cider. These were separated into neutral lipids (NL) and PL, while all lipid extracts were further assessed for their ability to inhibit aggregation of human platelets induced by PAF and ADP. In all cases, PL exhibited the strongest anti‐platelet bioactivities and were further separated by high‐performance liquid chromatography (HPLC) analysis into PL subclasses/fractions that were also assessed for their antiplatelet potency. The PL from low in tannins apple juice exhibited the strongest an‐ tiplatelet effects against PAF and ADP, while PL from its fermented cider product were less active. Moreover, the phosphatidylcholines (PC) in apple juices and the phosphatidylethanolamines (PE) in apple ciders were the most bioactive HPLC‐derived PL subclasses against PAF‐induced platelet aggregation. Structural elucidation of the fatty acid composition by gas chromatography mass spectra (GCMS) analysis showed that PL from all samples are rich in beneficial monounsaturated fatty acids (MUFA) and omega 3 (n‐3) polyunsaturated fatty acids (PUFA), providing a possible explanation for their strong anti‐platelet properties, while the favorable low levels of their ome‐ ga‐6/omega‐3 (n‐6/n‐3) PUFA ratio, especially for the bioactive PC and PE subclasses, further support an anti‐inflammatory cardio‐protective potency for these apple products. In conclusion, Irish apple juice and Real Irish cider were found to possess bioactive PL compounds with strong antiplatelet and anti‐inflammatory properties, while fermentation seems to be an important mod‐ ulating factor on their lipid content, structures and bioactivities. However, further studies are needed to evaluate these effects

Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism

<p>Abstract</p> <p>Background</p> <p>Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested. In this study we investigated the effect of fish polar lipid consumption on PAF metabolism.</p> <p>Results</p> <p>The specific activities of four PAF metabolic enzymes; in leukocytes, platelets and plasma, and PAF concentration; either in blood cells or plasma were determined. Samples were acquired at the beginning and at the end of a previously conducted study in male New Zealand white rabbits that were fed for 45 days with atherogenic diet supplemented (group-B, n = 6) or not (group-A, n = 6) with gilthead sea bream (<it>Sparus aurata</it>) polar lipids.</p> <p>The specific activity of PAF-Acetylhydrolase (PAF-AH); a catabolic enzyme of PAF, was decreased in rabbits' platelets of both A and B groups and in rabbits' leukocytes of group A (p < 0.05). On the other hand the specific activity of Lipoprotein-associated Phospholipase A2 (Lp-PLA2); the catabolic enzyme of PAF in plasma was increased in both A and B groups in both leukocytes and platelets (p < 0.05). PAF-cholinephosphotransferase (PAF-CPT); a biosynthetic enzyme of PAF showed increased specific activity only in rabbits' leukocytes of group A (p < 0.05). Neither of the two groups showed any change in Lyso-PAF-acetyltransferase (Lyso-PAF-AT) specific activity (p > 0.05). Free and bound PAF levels increased in group A while decreased in group B (p < 0.05).</p> <p>Conclusions</p> <p>Gilthead sea bream (<it>Sparus aurata</it>) polar lipids modulate PAF metabolism upon atherosclerotic conditions in rabbits leading to lower PAF levels and activity in blood of rabbits with reduced early atherosclerotic lesions compared to control group.</p

Structurally Diverse Metal Coordination Compounds, Bearing Imidodiphosphinate and Diphosphinoamine Ligands, as Potential Inhibitors of the Platelet Activating Factor

Metal complexes bearing dichalcogenated imidodiphosphinate [R2P(E)NP(E)R2′]− ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar [Cu{(OPPh2)(OPPh2)N-O, O}2], tetrahedral [Zn{(EPPh2)(EPPh2)N-E,E}2], E = O, S, and octahedral [Ga{(OPPh2)(OPPh2)N-O,O}3], were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar [Ni{(Ph2P)2N-S-CHMePh-P, P}X2], X = Cl, Br, the corresponding metal salts of all complexes and the (OPPh2)(OPPh2)NH ligand were also investigated. Ga(O,O)3 showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereas Zn(S,S)2, with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition. Zn(O,O)2 and Cu(O,O)2 inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkier Ga(O,O)3 being the most efficient and selective inhibitor

Characterization of the De Novo Biosynthetic Enzyme of Platelet Activating Factor, DDT-Insensitive Cholinephosphotransferase, of Human Mesangial Cells

Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+ and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass “Dicentrarchus labrax,” and gilthead sea bream “Sparus aurata”). The results indicated that the above compounds can influence PAF-CPT activity of HMC

Phytotoxins Produced by Fungi Associated with Grapevine Trunk Diseases

Up to 60 species of fungi in the Botryosphaeriaceae family, genera Cadophora, Cryptovalsa, Cylindrocarpon, Diatrype, Diatrypella, Eutypa, Eutypella, Fomitiporella, Fomitiporia, Inocutis, Phaeoacremonium and Phaeomoniella have been isolated from decline-affected grapevines all around the World. The main grapevine trunk diseases of mature vines are Eutypa dieback, the esca complex and cankers caused by the Botryospheriaceae, while in young vines the main diseases are Petri and black foot diseases. To understand the mechanism of these decline-associated diseases and the symptoms associated with them, the toxins produced by the pathogens involved in these diseases were isolated and characterised chemically and biologically. So far the toxins of only a small number of these decline fungi have been studied. This paper presents an overview of the toxins produced by the most serious of these vine wood pathogens: Eutypa lata, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and some taxa in the Botryosphaeriaceae family, and examines how these toxins produce decline symptoms. The chemical structure of these metabolites and in some cases their vivotoxin nature are also discussed