bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitation by radioimmunoassay of PAF in human saliva
Authors: Cooney Sue J. , Smal Mary A. , Baldo Brian A. 
Published: February 2007

AbstractApproximately 75% of the PAF present in saliva is recovered on extraction of whole saliva (0.8 vol) with chloroform/methanol/water (2∶2∶1 v/v/v). PAF levels, determined by our recently developed radioimmunoassay, in saliva extracts ranged from 0.5–21 ng/mL with 59% between 2–6 ng/mL. These figures, for apparently healthy subjects, are higher than previously reported levels obtained by platelet assays. The validity of our radioimmunoassay results was checked by isolating and quantitating the PAF fraction from whole saliva. In addition, when we examined our saliva samples by platelet aggregation, low levels of PAF, comparable with the values found in the literature, were detected. Investigations revealed the presence of a substance(s) which inhibited PAF‐induced platelet aggregation but which did not affect the radioimmunoassay.
Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine
Authors: Motasim Billah M. , Egan Robert W. , Ganguly Ashit K. , Green Michael J. , Kreutner William , Piwinski John J. , Siegel Marvin I. , Villani Frank J. , Wong Jesse K. 
Published: February 2007

AbstractFrom a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet‐activating factor (PAF) and histamine antagonist, Sch 37370, namely 1‐acetyl‐4‐(8‐chloro‐5,6‐dihydro‐11H‐benzo‐[5,6]cyclohepta[1,2‐b]pyridin‐11‐ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF‐induced aggregation of human plateletsin vitro (IC50=0.6 μM), andin vivo inhibits PAF‐ and histamine‐induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.
Pharmacological properties of YM461, a new orally active platelet‐activating factor antagonist
Authors: Yamada Toshimitsu , Saito Munetoshi , Mase Toshiyasu , Hara Hiromu , Nagaoka Hitoshi , Murase Kiyoshi , Tomioka Kenichi 
Published: February 2007

AbstractThe antagonistic effect of YM461 [1‐(3‐phenylpropyl)‐4‐[2‐(3‐pyridyl)thiazolidin‐4‐ylcarbonyl]piperazine fumarate] against platelet‐activating factor (PAF) was examined in severalin vitro andin vivo systems. We found that YM461 inhibited [3H]PAF binding to rabbit platelet membranes with a pKi value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA2 values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10−4M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED50 (50% effective dose) value of 0.35 mg/kgp.o. YM461 at doses above 0.3 mg/kgi.v. inhibited PAF induced hypotension in rats. YM461 showed a dose‐dependent inhibition of PAF induced hemoconcentration in rats with ED50 values of 0.15 and 0.21 mg/kgp.o., respectively, at 0.5 and 1 hr after oral administration. The anti‐PAF effect of YM461 persisted more than 6 hr after 3 mg/kgp.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED50 value of 1.2 mg/kgp.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kgp.o. significantly inhibited antigen‐induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist.
Bioactions of 5‐hydroxyicosatetraenoate and its interaction with platelet‐activating factor
Authors: Rossi Adriano G. , O'Flaherty Joseph T. 
Published: February 2007

AbstractIn a variety of stimulated cells, platelet‐activating factor (PAF) and numerous arachidonate derivatives are coproducts that form as a consequence of receptor‐mediated phospholipid mobilization. These lipid co‐products produce a plethora of biological effects in a wide variety of cell systems. Furthermore, they often have a fascinating, although less widely appreciated, interaction. 5‐HETE, at submicromolar concentrations, exerts relatively few direct bioactions. It does, however, potently (16–160 nM) raise cytosolic free calcium [Ca2+]i and augment PAF‐induced responses in human polymorphonuclear neutrophils (PMN) by as much as 100‐ to 1000‐fold. 5‐HETE acts on PMN by a structurally specific, stereospecific and pertussis toxin‐inhibitable mechanism. In addition, PMN exposed to 5‐HETE exhibit homologous but not heterologous desensitization. These findings suggest that 5‐HETE, like PAF, may bind to its own specific plasmalemmal receptors to exert its unique set of bioactions. However, further investigation is required to demonstrate any putative 5‐HETE receptors. Other potential mechanisms of 5‐HETE‐induced bioactions together with the possible effects of 5‐HETE on PAF transduction mechanisms are also discussed.
Platelet‐activating factor and polyunsaturated fatty acids in cerebral ischemia or convulsions: Intracellular PAF‐binding sites and activation of a fos/jun/AP‐1 transcriptional signaling system
Authors: Bazan Nicolas G. , Squinto Stephen P. , Braquet Pierre , Panetta Thomas , Marcheselli Victor L. 
Published: February 2007

AbstractPlatelet‐activating factor (PAF) is a lipid mediator formed in the early response of the central nervous system to ischemia or convulsions. Free polyunsaturated fatty acids and arachidonic and docosahexaenoic acids are accumulated along with PAF. Antagonists of PAF have been found to improve cerebral blood flow and partially block the rise in free fatty acids, an effect that may arise by way of inhibition of PAF receptors or stimulation of the reacylation of free fatty acids released upon insult. Three intracellular PAF‐binding sites have been identified in rat cerebral cortex. These very high‐affinity binding sites are inhibited by PAF antagonists, with certain antagonists exhibiting specificity for a particular binding site. This specificity indicates heterogeneity in these binding sites. Ischemia or stimulation also leads to protooncogene transcriptional activation. Here, we discuss studies with cells in culture showing that PAF promotes transcriptional activation of immediate‐early genes. PAF activates the transcription of the immediate‐early genesfos andjun, whose gene products are regulators of the transcription of other genes. Transcription offos is also activated by convulsion or ischemia in the central nervous system. The activation of these genes by PAF can be inhibited by PAF antagonists, and is apparently accomplished by way of an AP‐1 transcription regulatory sequence in the promoter region of the target genes. Studies with deletion mutants show that PAF can also exert its activating properties by way of cyclic adenosine‐3′,5′‐monophosphate‐(cAMP) and Ca2+‐responsive elements, and suggest that PAF is involved in an interconnected network of cell signaling that may coordinate short‐term and long‐term responses of cells to stimulus and injury.
Cardiovascular effects of platelet‐activating factor
Authors: Goldstein Robert E. , Feuerstein Giora Z. , Bradley Linda M. , Stambouly Joseph J. , Laurindo Francisco R. M. , Davenport Nancy J. 
Published: February 2007

AbstractSudden release of platelet‐activating factor (PAF) into the circulation can cause hypotension, tachycardia, and circulatory collapse. To further examine this response, we performed detailed studies of cardiovascular function after PAF administration to young domestic pigs and newborn piglets. Our results indicate that circulatory dysfunction after PAF reflects severe constriction of pulmonary resistance vessels and consequent acute right ventricular failure. Although PAF‐induced coronary artery constriction and contractile depression may be complicating problems, left ventricular underperfusion and dysfunction after PAF are mainly the result of systemic arterial hypotension and diminished left ventricular filling. The adverse hemodynamic effects of PAF are accompanied by substantial release of thromboxane A2 (TxA2). These effects are mimicked by the TxA2 agonist U‐46619 and partially blocked by specific and nonspecific inhibitors of TxA2 synthesis (OKY‐046 and indomethacin). Even more potent blockade of PAF action is exerted by the TxA2 receptor blocker, SQ 29,548. Taken together, these findings indicate that severe pulmonary vascular constriction and hemodynamic collapse soon after intravenous PAF are at least partially mediated by PAF‐induced TxA2 release.Tachyphylaxis to PAF influence has been observed in studies of leukocyte and platelet function. We hypothesized that tachyphylaxis to PAF might also occur in our studies of constrictor responses in pulmonary vessels. Recently, we have examined the capacity of PAF to produce sustained pulmonary vasoconstriction in openchested, anesthetized newborn piglets. Infusions sufficient to produce 100% increase in mean pulmonary artery pressure after 3 min showed no loss of efficacy when sustained for 30 min. The same was true for infusions of U‐46619. Thus, the pulmonary vasoconstrictor influence of PAF or U‐46619 is not readily diminished by tachyphylaxis. These findings favor the viewpoint that PAF or TxA2 release during inflammatory processes could have prolonged adverse actions on pulmonary and systemic circulations.
Role for platelet‐activating factor in asthma
Authors: Chung K. F. , Barnes P. J. 
Published: February 2007

AbstractRecent studies of the effects of platelet‐activating factor (PAF) on huan and animal airways would support a putative role for this lipid mediator in asthma. PAF can induce many aspects of the clinical and pathological features seen in asthmatic airways such as airway oedema, eosinophil accumulation in the airway wall, and bronchial hyperresponsiveness. PAF has potent activity as a chemotactic agent and as an activator of eosinophils, which are prominent cells in asthmatic airways, through the activation of specific surface receptors. The interaction between PAF and eosinophils may be crucial in the pathogenesis of bronchial hyperresponsiveness in asthma. A role for PAF in asthma can now be studied using the recently developed antagonists of the PAF receptor.
Platelet‐activating factor detected in bronchoalveolar lavage fluids from an asthmatic patient
Authors: Horii Tsugio , Okazaki Hitoshi , Kino Minoru , Kobayashi Yohnosuke , Satouchi Kiyoshi , Saito Kunihiko 
Published: February 2007

AbstractIt recently has been recognized that platelet‐activating factor (PAF) may be a mediator of asthma exacerbation. We had the opportunity to analyze bronchoalveolar lavage fluids from an asthmatic infant, which were characterized by neutrophil infiltration. The patient's lungs were washed on three occasions with saline during asthmatic attacks. PAF was found in each case on the basis of its ability to cause the immediate aggregation of washed rabbit platelets. The PAF detected was equivalent to 1–1.4 pmol of 1‐O‐hexadecyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine, three quarters of which were recovered in cell‐associated form. By contrast, we did not detect PAF in bronchoalveolar exudates from patients with larungeal stenosis or with respiratory distress syndrome. LysoPAF, the direct precursor as well as initial metabolite of PAF, was also analyzed after being converted to PAF by acetylation. There was a wide variation in the amount of lysoPAF present in individual patients, suggesting that lysoPAF levels cannot be taken as an indicator for the presence of PAF.
Platelet‐activating factor (PAF) in allergic diseases: Inhibitory effects of anti‐allergic drugs, ketotifen and three Kampo medicines on PAF production
Authors: Nakamura Tsuneyoshi , Kuriyama Motoaki , Ishihara Keiko , Matsumura Yukio , Miyamoto Terumasa 
Published: February 2007

AbstractPlatelet‐activating factor (PAF) is considered an important mediator in allergic and inflammatory reactions. To further investigate the role of PAF in allergic diseases, we examined thein vitro andex vivo effect of anti‐allergic drugs on PAF production by human neutrophils. Ketotifen and three Kampo medicines, which are widely used in the treatment of allergic diseases in Japan, inhibited PAF production by normal human neutrophils dose‐dependently, whereas disodium chromoglycate (DSCG) and tranilast did not have any inhibitory effect. Ketotifen also suppressedex vivo PAF production by neutrophils from healthy subjects. PAF production decreased from 40.5±5.0 units to 21.6±4.7 units after oral administration of 2 mg of ketotifen per day for one week. We also measured the concentration of lysoPAF in serum from patients with Japanese cedar pollinosis during the pollen season and followed the effect of ketotifen on lysoPAF levels in the serum from these patients. We found that the concentration of lysoPAF, a precursor and degradation product of PAF, in patients with cedar pollinosis (87.8±8.7 units) was significantly higher than in healthy subjects (54.7±7.7 units). After two weeks, lysoPAF levels decreased significantly (82.6 units to 41.3 units) only in the group treated with nasal aerosol and ketotifen. These results suggest that PAF may play a role in allergic diseases and that the clinical effects of anti‐allergic drugs may at least partially be due to their anti‐PAF action.
Effect of the selective PAF antagonist SM‐10661 on an asthmatic model. 1. Effect on passive anaphylactic bronchoconstriction in guinea pigs
Authors: Uchida Masako , Imanishi Noriaki , Sugasawa Toshinari , Morooka Shigeaki 
Published: February 2007

AbstractThe effect of SM‐10661, a selective antagonist of platelet‐activating factor (PAF), on passive anaphylactic bronchoconstriction was examined in guinea pigs. A challenge of ovalbumin to passively sensitized guinea pigs induced bronchoconstriction, which peaked at 4 min. When SM‐10661 was administered intravenously 2 min before ovalbumin challenge, bronchoconstriction was inhibited dose‐dependently with an ID50 of 68 mg/kg. In guinea pigs pretreated with 15 μg/kg mepyramine which is a suboptimal dose, antigen‐induced bronchoconstriction peaked at 4–6 min, but was inhibited by SM‐10661 with an ID50 of 21 mg/kg. When guinea pigs were pretreated intravenously with 2.5 mg/kg mepyramine, 1 mg/kg indomethacin and 0.01 mg/kg propranolol, the antigen‐induced bronchoconstriction peaked at 6 min. SM‐10661 inhibited the response with an ID50 of 45 mg/kg. Histamine‐ and leukotriene D4‐induced bronchoconstrictions were unaffected by up to 100 mg/kg SM‐10661. Ovalbumin challenge of minced lungs from passively sensitized guinea pigs triggered the release of leukotrienes and histamine. SM‐10661 had no effect on the antigen‐induced release of peptide leukotrienes or histamine up to 10−4 M. These results indicate that SM‐10661 may be a useful tool to investigate the role of PAF in antigen‐induced anaphylactic bronchoconstriction.
Effect of platelet‐activating factor antagonist BN 52063 on the nephrotoxicity of cisplatin
Authors: Pavão dos Santos Oscar F. , Boim Mirian A. , Barros Elivo J. G. , Pirotzky Eduardo , Braquet Pierre , Schor Nestor 
Published: February 2007

AbstractCisplatin (DDP) is an effective anticancer agent that has been successfully applied against various solid tumors. However, DDP commonly causes nephrotoxicity. We observed that DDP led to significant alterations in renal microcirculation when administered to Munich‐Wistar rats, with a concomitant decrease in single nephron glomerular filtration rate due to reduction in glomerular plasma flow and transcapillary hydraulic pressure difference. BN 52063, a platelet‐activating factor antagonist, caused a striking change in acute renal failure induced by DDP leading toward normalization of all parameters of renal function. The results suggest that BN 52063 could be used as a novel drug to control DDP nephrotoxicity.
Significance of platelet‐activating factor in mesenteric ischemia‐reperfusion
Authors: Filep János , Braquet Pierre , Mózes Tibor 
Published: February 2007

AbstractReperfusion of the ischemic mesenterium is frequently followed by acute circulatory collapse. This review focuses on the possible role of platelet‐activating factor (PAF) in ischemia‐induced damage. It provides evidence that (i) PAF concentrations are elevated in the mesenteric circulation following temporary ischemia; (ii) administration of exogenous PAF into the superior mesenteric vein mimics many events observed during reperfusion; and (iii) pretreatment of the experimental animals with specific PAF receptor antagonists prevent the circulatory collapse. These findings suggest that PAF may play an important role in the development of circulatory collapse caused by mesenteric ischemia‐reperfusion.
Hypoxia, PAF, and necrotizing enterocolitis
Authors: Caplan Michael S. , Sun Xiao‐Ming , Hsueh Wei 
Published: February 2007

AbstractNecrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate. The pathophysiology is unclear but epidemiologic studies suggest that hypoxia and infection are important risk factors. In this review we discuss the effect of hypoxia and platelet‐activating factor (PAF) on intestinal blood flow and intestinal necrosis, and implicate PAF as an important mediator in hypoxia‐induced intestinal injury. Finally we provide evidence that PAF may be important in neonatal NEC.
Antagonism of platelet‐activating factor in isolated rat colon: Possible mechanism
Authors: Tokumura Akira , Yube Nobuyuki , Terao Motonori , Tsukatani Hiroaki 
Published: February 2007

AbstractThe contractions of three different regions of rat colon in response to platelet‐activating factor (PAF) were compared. The ascending colon was found to be the most responsive. The slow contraction of the ascending colon induced by PAF was dependent on external Ca2+. CV‐3988, a structural analog of PAF, slowly induced irreversible inhibition of PAF‐induced contraction, whereas FR‐900452, which is structurally unrelated to PAF, caused rapid reversible inhibition of PAF‐induced contraction. No inhibitory effects of CV‐3988 were observed when the strip was washed with Tyrode's solution containing 1% bovine serum albumin (BSA). The results suggest that PAF and CV‐3988 penetrate slowly into the outer half of the lipid bilayer of plasma membranes of cells in isolated rat colon, and then rapidly diffuse laterally to associate firmly with specific binding sites.
Molecular heterogeneity of platelet‐activating factor (PAF) in rat glandular stomach determined by gas chromatography/mass spectrometry. PAF molecular species changes upon water‐immersion stress
Authors: Sugatani Junko , Fujimura Kazuyo , Miwa Masao , Satouchi Kiyoshi , Saito Kunihiko 
Published: February 2007

AbstractThe molecular heterogeneity of 1‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine (alkylacetyl‐GPC) and 1‐acyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine (acylacetyl‐GPC) in normal rat glandular stomach was studied by gas chromatography/mass spectrometry (GC/MS) and tandem mass spectrometry. The percentage compositions of the molecular species of 1‐alkyl‐2‐acetyl‐GPC and 1‐acyl‐2‐acetyl‐GPC in the antrum were, respectively. 1‐alkyl [16∶0 (34%) and 18∶0 (66%)]‐2‐acetyl‐GPC and 1‐acyl [16∶0 (60%), 18∶0 (14%) and 18∶1 (26%)]‐2‐acetyl‐GPC. The alkyl chain composition of 1‐alkyl‐2‐acyl‐GPC was quite different from that of 1‐alkyl‐2‐acyl‐GPC in both the antrum and corpus, demonstrating a high degree of selectivity of alkyl chain utilization in PAF biosynthesis. The amount of 1‐acyl‐2‐acetyl‐GPC was much greater than that of 1‐alkyl‐2‐acetyl‐GPC. The molecular heterogeneity of 1‐alkyl‐2‐acetyl‐GPC and 1‐acyl‐2‐acetyl‐GPC in the corpus was similar to that in the antrum. Water‐immersion stress affected not only the amount of 1‐alkyl‐2‐acetyl‐GPC and 1‐acyl‐2‐acetyl‐GPC, but also their molecular heterogeneity in the antrum and corpus. Whereas the amounts of 1‐hexadecyl‐2‐acetyl‐GPC and 1‐acyl [16∶0, 18∶0 and 18∶1]‐2‐acetyl‐GPC decreased markedly (to less than one‐fifth) in the antrum after such stress for 1 hr, the amount of 1‐octadecyl‐2‐acetyl‐GPC increased markedly (up to 4‐fold) in the corpus and severe lesions were observed after stress for 7 hr. The changes may be associated with the pathogenicity of gastric ulcers.
Platelet‐activating factor and granulocyte‐mediated oxidative stress. Strategy forin vivo oxyradical visualization
Authors: Suematsu Makoto , Tsuchiya Masaharu 
Published: February 2007

AbstractPlatelet‐activating factor (PAF) and leukotriene B4 are potent lipid mediators of endothelium‐granulocyte interaction which results in granulocyte‐dependent increased microvascular permeability. The specific mechanism by which PAF induces granulocyte‐mediated endothelial injury has not been fully investigated. Digital imaging photonic intensified microscopy has revealed that PAF effectively induces granulocyte‐mediated oxidative stress on microvascular beds. The method has made it possible to visualize luminol‐dependent photonic burst released from PAF‐treated microvascular beds in the rat mesentery. The photonic activities clearly corresponded to the localization of sticking granulocytes in post‐capillary venules. By contrast, no significant chemilumigenic response could be detected in the leukotriene B4‐induced activation of endothelium‐granulocyte interactionin vivo. The present findings suggest that oxygen radicals are not prerequisites for granulocyte adhesion in the microcirculation and provide evidence for a dissociation ofin vivo granulocyte function between leukotactic and oxidative activation in leukotriene B4‐induced microvascular changes.
Involvement of platelet‐activating factor (PAF) in septic shock and priming as indicated by the effect of hetrazepinoic PAF antagonists
Authors: Heuer Hubert O. 
Published: February 2007

AbstractPharmacological data obtained with hetrazepinoic platelet‐activating factor (PAF) antagonists, such as apafant (WEB 2086) and bepafant (WEB 2170), indicate a role for PAF in septic shock and in the priming process. The effect of PAF antagonists in different models of shock states favors a role for PAF in endotoxin associated lethality, activation of inflammatory blood cells with release of mediators, cardiovascular failure and increased vascular permeability, and in the development of shock organs and organ failure. The priming process (e.g., by endotoxin or tumor necrosis factor) towards an increased susceptibility towards minute amounts of PAF has to be taken into account when considering the pathophysiological significance of PAF underin vivo conditions and in septic shock.