Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of platelet-activating factor (PAF) in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring PAF levels in the superior mesenteric vein during reperfusion after 2-h occlusion of the superior mesenteric artery; by monitoring the effects of BN 52021, a specific PAF receptor antagonist; and by studying the circulatory effects of exogenous PAF injected into the superior mesenteric vein. PAF was measured by a platelet-aggregation assay. Identity of PAF-like bioactivity was ascertained by thin-layer chromatography, high-pressure liquid chromatography, and alkaline treatment. Removal of the superior mesenteric artery occlusion caused an immediate dramatic decrease in mean arterial blood pressure with concomitant increase in mean portal venous pressure and hematocrit values. PAF concentration in the superior mesenteric vein increased from 0.2 +/- 0.1 to 2.8 +/- 0.4 ng/ml (n = 4, P less than 0.05) within the first 5 min of reperfusion. Administration of exogenous PAF (0.1 microgram/kg) injected into the superior mesenteric vein produced similar hemodynamical effects. Pretreatment of the animals with BN 52021 (4 mg/kg), a specific PAF receptor antagonist, prevented the circulatory collapse. The present results suggest that PAF release during intestinal ischemia may play an important role in the development of circulatory collapse caused by mesenteric artery occlusion.
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PMID:Platelet-activating factor: an endogenous mediator of mesenteric ischemia-reperfusion-induced shock. 280 4

We treated four anesthetized dogs (Canis familiaris) with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous 111In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone (3 mg/kg) administered 5 min prior to ischemia and continuously (1 mg/kg/hr) throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude (% of baseline) when compared to controls (27-36% vs 9-14%, p less than 0.05). We estimated platelet accumulation as 111In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered 111In-labeled platelet accumulation when compared to controls (6158 +/- 2386 vs 9979 +/- 3852, mean +/- SEM). Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved.
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PMID:Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia. 282 47

The possible role of platelet-activating factor (PAF) in superior mesenteric artery occlusion induced circulatory collapse was studied in anesthetized dogs. PAF was measured by platelet aggregation assay. Identity of PAF-like product in blood was ascertained by thin layer chromatography, high pressure liquid chromatography and alkaline treatment. Low amount of PAF was detected in the mesenteric blood under normal conditions, during reperfusion PAF levels were significantly higher. Pretreatment of the animals with BN 52021, a specific PAF receptor antagonist abolished the fall in mean arterial pressure and the rise in hematocrit due to ischemia/reperfusion. These findings suggest that PAF may play an important role in mesenteric ischemia-induced circulatory collapse.
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PMID:Increased levels of platelet-activating factor in blood following intestinal ischemia in the dog. 291 86

The effect of the platelet activating factor (PAF) antagonist BN52021 on [3H]D-aspartate (D-Asp) release was investigated in rat hippocampal slices during and after incubation (20 min) in ischaemia-like conditions. Ischaemia did not influence spontaneous D-Asp outflow whereas K(+)-evoked, calcium-dependent release was markedly enhanced in reoxygenated, post-ischaemic slices. These slices also showed a substantial translocation/activation of protein kinase C (PKC). BN52021 blocked both ischaemia-induced effects. Moreover, the PKC inhibitor H7 attenuated post-ischaemic K(+)-evoked D-Asp release when beta-PDBu, a PKC activator, was used to enhance the response of normoxic slices. Assuming that PKC is activated by ischaemia in a PAF-dependent manner and that this activation proceeds to enhanced glutamate exocytosis, we speculate on the involvement of PAF receptor stimulation in the pathology of cerebral ischaemia.
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PMID:PAF antagonist, BN52021, inhibits [3H]D-aspartate release after ischaemia in vitro. 770 35

Our in vivo model of mesenteric ischemia/reperfusion (I/R) has shown that the gut serves as a priming bed for neutrophils (PMN). Activation of phospholipase A2 (PLA2) during ischemia temporally precedes PMN sequestration in the gut and the appearance of primed PMN in the portal circulation. Therefore, we hypothesized that reperfused gut secretes platelet activating factor (PAF) via PLA2 activation that is responsible for increased PMN chemotaxis and priming for superoxide (O2-) generation. Sprague-Dawley rats underwent gut ischemia/reperfusion (45 min SMA occlusion/2 hr reperfusion) or sham laparotomy. Distal ileum was harvested, rinsed with bacteriostatic saline/neomycin, and incubated for 1 hr at 37 degrees C in RPMI 1640 and the cell-free supernatant was collected. Normal human PMNs, isolated by plasma-Percoll gradients, were pretreated with or without a PAF receptor antagonist (WEB 2170). Chemotaxis toward gut supernatant was then measured by the agarose method. Additionally, PMNs were preincubated with or without WEB 2170 and their O2- release in response to 1 microM FMLP was measured by the Vmax of SOD-inhibitable cytochrome c reduction. Reperfused gut produced a chemotactic index of 2.1 +/- 0.1 compared to 0.2 +/- 0.9 following sham laparotomy (P < 0.05); this was reduced to 0.4 +/- 0.9 with PAF receptor blockade. Similarly, gut I/R supernatant primed PMNs for O2- (P < 0.05) compared to laparotomy, and this effect was abrogated by a PAF antagonist. These data suggest that reperfused gut can elaborate PAF which chemoattracts and primes PMNs for O2- generation.
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PMID:Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. 779 40

Platelet activating factor is a unique phosphoglycerine which possesses a variety of biological functions exerting its biological effects via specific surface receptors. In the central nervous system, platelet activating factor has been suggested to play a role during injury especially in conditions of ischemia and trauma-induced neuronal damage. The specific cell populations expressing platelet activating factor receptor, however, have not been identified. In this study, the binding properties of platelet activating factor receptors in C6 glioma cells and primary cultures of astrocytes and oligodendrocytes were characterized by using the ligand [3H]WEB 2086. Early-passage glial cells which exhibit oligodendrocytic phenotype, expressed lower levels of [3H]WEB 2086 binding than either late-passage cells which exhibit astrocytic phenotypes or primary astroglia cells. No specific binding was observed in primary cultures of oligodendrocytes. The Bmax (136 +/- 15.3 fmol/mg protein) and Kd (29 +/- 3.2 nM) levels obtained for primary astroglia cells were similar to those described for other cell types. The expression of platelet activating factor receptor in early-passage glia cells was up-regulated by treatment with insulin which induces astrocytic differentiation. In contrast, db-cyclic AMP exerted an inhibitory effect on the level of platelet activating factor receptor in both early- and late-passage cells. The level of functional platelet activating factor receptor in C6 cells as measured by the ability of platelet activating factor to induce 45Ca2+ influx was increased in cells expressing astrocytic phenotypes and was decreased in db-cyclic AMP-treated cells. In accordance with lack of specific [3H]WEB 2086 binding, platelet activating factor did not induce a detectable response of Ca2+ influx in cultures of oligodendrocytes. This report provides the first direct demonstration of selective expression of functional platelet activating factor receptors and their properties in astroglia cells. The findings support the suggestion that platelet activating factor may play an important role as a mediator of injury and immune responses in the nervous system.
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PMID:Functional PAF receptors in glia cells: binding parameters and regulation of expression. 790 May 45

Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]) is a potent lipid autocoid produced by many cell types. PAF is produced by cultured rat cerebellar neurons and human fetal brain cells, and has been extracted from brain tissue. Multiple PAF receptors have been demonstrated in brain tissue. PAF stimulates intracellular Ca2+ mobilization and phosphatidylinositol (PI) metabolism in transformed neuronal cell lines via the PAF receptor, to which both pertussis toxin (PTX)-sensitive and -insensitive G protein appear to couple. PAF has potent actions on cerebral vessels and cerebral metabolism when administered in vivo. Direct neuronal effects of PAF, such as inhibition of acetylcholine release, are observed in vitro. Excessive PAF production in pathological states of the nervous system, such as neurotrauma and stroke, has been shown. In multiple studies in rodent and non-rodent models using highly specific and potent PAF antagonists, reversal or prevention of key consequences of brain injury, such as hypoperfusion following ischemia, reperfusion and edema, inflammatory cell accumulation, neurologic/motor deficits, and neuronal salvage, has been demonstrated. These studies taken together support a role for PAF as an important mediator in the pathophysiology of brain injury.
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PMID:Platelet-activating factor: a putative neuromodulator and mediator in the pathophysiology of brain injury. 790 80

Platelet-activating factor (PAF) is a powerful lipid autacoid with a variety of biological activities. More and more evidence suggests that PAF might play an important role in modulation of cerebrovascular system function, particularly during ischemia-induced cerebrovascular damage. However, the mechanisms involved in PAF actions on cerebrovascular or other brain cells are virtually unknown. Therefore, this study was designed to investigate PAF receptor-mediated cellular signal transduction in bovine cerebral microvascular endothelial (CME) cells with the aid of a potent PAF antagonist, WEB 2086. PAF induced an immediate and concentration-dependent increase in [Ca2+]i with an EC50 of 4.75 nM. PAF-induced [Ca2+]i mobilization was inhibited by PAF antagonist WEB 2086, in a dose-dependent manner (IC50 = 15.53 nM). The calcium channel blockers diltiazem (10 microM) and verapamil (10 microM) had no effect on the PAF-induced increase in [Ca2+]i, but depletion of Ca2+ from the incubation buffer caused a 45.26% reduction of PAF-induced [Ca2+]i elevation. PAF stimulated phosphoinositide metabolism in a dose-dependent manner with an EC50 of 12.4 nM for IP3 formation, which was also inhibited by the PAF antagonist WEB 2086 in a dose-dependent manner with IC50 value of 16.97 nM for IP3 production. These data indicate that bovine CME cells respond to biologically relevant concentrations of PAF and this response involves activation of phospholipase C and increase in [Ca2+]i via specific PAF receptors. Our results may contribute to further understanding of the mechanism behind PAF actions on cerebrovascular cells.
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PMID:Platelet-activating factor induced calcium mobilization and phosphoinositide metabolism in cultured bovine cerebral microvascular endothelial cells. 798 Dec 48

In a model of intestinal ischemia-reperfusion resulting in hypotension, mucosal lesions in the small intestine and mortality, the effects of a combination of superoxide dismutase (SOD) and catalase (cat) or a PAF receptor antagonist were tested. Intestinal ischemia was induced in rats and continued for 60 min. After this, the intestine was reperfused. A PAF receptor antagonist, BN 52021, was given 50 min before ischemia in one group, and SOD + cat was given 10 min before reperfusion in one group. One group received normal saline and one group were controls. Blood pressure, mucosal lesions, plasma volume, and endotoxin in plasma were determined up to 3 hr after reperfusion. Mortality was determined over 4 days. Endogenous endotoxin was not found in any of the groups, but the first types of SOD and cat used were contaminated with endotoxin, resulting in exogenous endotoxemia in animals which received those substances. Later endotoxin-free enzymes were used. Neither SOD + cat nor PAF antagonist had any effect on the hypotension or mucosal lesions. Plasma volume remained at the level of the control group after administration of either regimen. Mortality decreased in the group that received SOD + cat. The effects of SOD + cat indicate that free radicals were released in this model at reperfusion, and the effects of the PAF receptor antagonist indicate that PAF participates in membrane damage, but is an intermediary mechanism in the shock model used. The clearance of infused endotoxin from plasma was less effective in the shocked animals, possibly due to a shock effect on reticuloendothelial system (RES).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of antioxidants and PAF receptor antagonist in intestinal shock in the rat. 801 65

Ischemia is a well-known situation occurring in several diseases. There is a large body of evidence for the accumulation of neutrophils in the microvascular injury and the transformation of ischemic tissue into an inflammatory territory. However, the molecular mechanisms underlying this phenomenon are still poorly understood. The effects of hypoxia were investigated on human umbilical vein endothelial cells (HUVEC) in culture, and a very strong activation of these cells was obtained with an induction of the platelet-activating factor (PAF) synthesis which was optimal after 90 min of hypoxia. PAF was chemically identified by gas chromatography-mass spectrometry. Along with incubation under hypoxia, a constant increase in the adherence of unstimulated human polymorphonuclear neutrophils (PMN) to endothelial cells was observed. The role of PAF and of adhesion glycoproteins in this hypoxia-induced neutrophil adherence to HUVEC was then assessed. The adherence was mediated by PAF after 90 min of hypoxia as indicated by the inhibition obtained with PAF receptor antagonists and with PAF synthesis inhibition. When tested on HUVEC incubated for 120 min under hypoxia, PAF antagonists could not inhibit the PMN adherence, whereas inhibition of PAF during hypoxia could block the process, suggesting a role of PAF acting as a second messenger. In addition, the inhibitory effects obtained using monoclonal antibodies indicate that this increased adherence was also mediated by intracellular adhesion molecule 1 on HUVEC and by CD18/CD11b on neutrophils. GMP-140 seems also to be involved after 90 min hypoxia but not after 120 min hypoxia, which correlated well with the presence of PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased PMN adherence on endothelial cells after hypoxia: involvement of PAF, CD18/CD11b, and ICAM-1. 809 7


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