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 most prominent symptom of Shy-Drager syndrome is the asympathicotonic orthostatic (postural) hypotension, which is associated with a number of additional autonomic and neurological disturbances: disorders of micturition, sphincter disturbances, impotence, anhidrosis, hypokinesia, rigidity, pyramidal symptoms, cerebellar dysfunction and nuclear pareses due to anterior horn cell degeneration. The various disorders are not caused by ischemia or hypotension, but they represent parts of a multisystemic disease of still unknown etiology. According to different extension and neuropathological criteria it has been suggested to distinguish two types of neurogenic (idiopathic) orthostatic hypotension. Moreover, differential diagnosis of the Shy-Drager syndrome has to consider postural hypotension occuring as a symptom in some neuropathies and Parkinson's disease. Symptomatology, course, prognosis and treatment of Shy-Drager syndrome are described, as well as relevant findings of apparative investigations, pharmacological and hemodynamic tests and neuropathological findings in autopsied cases reported in the literature. This review was initiated by two clinically investigated cases of Shy-Drager syndrome.
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PMID:[The Shy-Drager syndrome (author's transl)]. 24 13

To determine the role of platelet-activating factor (1-O-hexa-decyl-2-acetyl-sn-glyceryl-phosphoryl-choline, PAF) in myocardial ischemic and reperfusion-induced injury, the effects of a PAF receptor antagonist (WEB 2086) were studied in an anesthetized canine model of ischemia (90 min) and reperfusion (6 h). Thirty minutes after onset of ischemia, WEB 2086 was administered as a bolus (20 mg/kg intravenously, i.v.) followed by a continuous 6-h infusion (10 mg/kg/h i.v.). Controls received vehicle alone (0.9% saline). Platelet aggregation was studied at baseline and at 1, 2, 4, and 6 h of drug administration and at the end of the reperfusion period. WEB 2086 treatment did not significantly affect platelet aggregation stimulated by ADP or arachidonic acid (AA). After 1 h of drug infusion, the ex vivo aggregatory response to exogenous (200 nM) PAF was ablated in WEB 2086-treated animals. WEB 2086 administration did not affect heart rate (HR) or mean arterial blood pressure (MAP) during the occlusion or reperfusion phases. During reperfusion of the ischemic tissue, left circumflex coronary artery (LCX) blood flow of WEB 2086-treated animals increased (p < 0.05) above control value. The area of the left ventricle at risk of infarct was not different between control and WEB 2086-treated groups. Infarct size was not significantly reduced in WEB 2086-treated animals. The results of our investigation using a 90-min ischemic period followed by 6-h reperfusion show that pharmacologic antagonism of PAF by WEB 2086 does not protect the heart against ischemia and reperfusion-induced injury.
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PMID:Inhibition of platelet-activating factor fails to limit ischemia and reperfusion-induced myocardial damage. 128 5

The intracellular accumulation of PAF following cell stimulation suggests an intracellular signal transduction pathway. High affinity binding sites for PAF in microsomal membranes and displacement of PAF from these sites by structurally distinct PAF antagonists suggests the existence of an intracellular receptor. Suppression of primary genomic responses by a PAF antagonist selective for the intracellular Ca2+ and arachidonic acid metabolites, is linking the intracellular generation of PAF to immediate-early transcription. Several of the metabolites that transiently accumulate after injury may elicit beneficial effects on regenerative processes. The membrane metabolite PAF, which accumulates after seizure and ischemia, may initiate reparative processes by promoting transcriptional activation of immediate-early transcription factors. The long-term effects of these immediate-early gene transcription factors may provide a synthetic mechanism to replenish and rebuild cells following traumatic events.
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PMID:Second messengers derived from excitable membranes are involved in ischemic and seizure-related brain damage. 130 97

The biologically active lipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine; PAF) is a mediator of inflammatory and immune responses, and it accumulates in the brain during convulsions or ischemia. We have examined whether PAF may play a second messenger role in the central nervous system by studying effects on synaptic transmission in cultured hippocampal neurons. Carbamyl-PAF, a nonhydrolyzable PAF analog with a similar pharmacologic profile, augmented glutamate-mediated, evoked excitatory synaptic transmission and increased the frequency of spontaneous miniature excitatory synaptic events without increasing their amplitude or altering their time course. This compound had no significant effect on gamma-aminobutyric acid-mediated inhibitory synaptic responses. Lyso-PAF, the biologically inactive metabolic intermediate, had no effect on synaptic transmission. Moreover, the enhancement of excitatory synaptic transmission by carbamyl-PAF was blocked by a PAF receptor antagonist. These results indicate a specific presynaptic effect of PAF in enhancing excitatory synaptic transmission in cultured rat hippocampal neurons.
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PMID:Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. 133 22

The vascular endothelium can be regarded as a widely distributed organ, interposed between the intravascular and extravascular spaces, with a pluripotent function in the regulation of capillary diameter, vascular homeostasis, lipoprotein metabolism and the vascular response to injury. In the basal physiological state these processes provide a non-thrombotic, non-inflammatory vascular lining preventing uncontrolled inflammation and coagulation. Endothelial cells respond to potential harmful conditions (mechanical stress, anoxia, ischemia and oxidative stress) and a variety of hormones and vasoactive mediators by inducing coagulation and production of inflammatory mediators through the production of 'bioactive' lipids. Although the number of studies in isolated myocardial endothelial cells is limited, from the presumed metabolic analogy with endothelial cells isolated (and cultured) from other organs, one may conclude that the bioactive lipids include oxygenated arachidonate metabolites (eicosanoids) and the platelet activating factor (1--O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF). All aspects of lipid metabolism, related to the production of eicosanoids and PAF, are present within myocardial endothelial cells. There is uptake and incorporation of fatty acids by endothelial cells and liberation from endogenous triacylglycerol and (membrane) phospholipid stores by (phospho)lipases. Endothelial cells oxidize fatty acids in a carnitine-dependent, mitochondrial, pathway. Endothelial cells actively interact with high density lipoprotein (HDL) and low density lipoprotein (LDL) leading to uptake of cholesterol(esters) that undergo intracellular hydrolysis, and re-esterification to phospho- and neutral lipids, and leaving the LDL-particle modified in a way that makes them bind to the scavenger receptor on macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipid metabolism of myocardial endothelial cells. 148 Jan 46

In addition to their traditional role in infection elimination and scavenging dead tissue, neutrophils may be injurious to myocardial tissues. Besides mechanical participation they produce toxic oxygen species, PAF, arachidonic acid metabolites, and release the proteases from intracellular granules. The deleterious role of PMN within myocardial ischemic focus depends also on the cooperation with platelets, macrophages, endothelial and mast cells. Rapid entry of neutrophils during ischemia contribute to arrhythmia, loss of coronary vasomotion, no-reflow phenomenon and extension of cellular injury. Further work is needed to define the precise role that neutrophils play in tissue injury and to propose an appropriate strategy by which PMN function can be modified to limit infarct size.
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PMID:The role of polymorphonuclear neutrophils in myocardial damage during ischemia and reperfusion. 148 26

The last two decades of research have produced detailed information not only on how ischemia causes degradation of phospholipids and accumulation of potentially cytotoxic breakdown products of such lipids, but also on reactions elicited by the subsequent conversion of these products into a series of lipids, mediating an array of cellular and intercellular reactions. It now seems clear that PAF, as well as several of the cyclooxygenase and lipoxygenase products of arachidonic acid, can induce changes, particularly in the microvasculature, which jeopardize cell survival in reperfused tissue. It is equally clear that, at least following long periods of ischemia, free radicals generated in reactions that are interacting with those producing eicosanoids and PAF play a similar role. A somewhat more speculative mechanism links sustained activation and membrane translocation of PKC to delayed neuronal death following transient ischemia. All of these interactions underscore the importance of lipolytic events for cell damage in ischemia and other conditions with a compromised cellular energy metabolism.
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PMID:Ischemic brain damage: focus on lipids and lipid mediators. 163 6

While it has been postulated that lyso-PAF and PAF might contribute to structural and functional damage in myocardial ischaemia, there has been no clear evidence for the accumulation of these bioactive compounds in ischaemic myocardium. In open chest, anaesthetised dogs, the proximal left anterior descending coronary artery was ligated and myocardial samples from the central ischaemic and normal areas assayed for lyso-PAF, free arachidonic acid and PLA2 activity. Ischaemic myocardium contained 50 +/- 29% (SD) more lyso-PAF than non-ischaemic myocardium after 20 min ischemia (P less than 0.002; N = 8) and 53 +/- 39% more after 60 min (P less than 0.01; N = 8) but there was no difference after 10 min (N = 8). Free arachidonic acid significantly increased in ischaemic myocardium after 60 min (122 +/- 136%; P less than 0.05) while no increase in PLA2 activity was found in-vitro. Since lyso-phospholipids themselves damage cell membranes and, additionally, lyso-PAF is the precursor of PAF which has potent effects on platelets, leukocytes and small vessels, the increase in lyso-PAF in ischaemic myocardium could contribute to myocardial damage.
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PMID:The lyso-precursor of platelet-activating factor (lyso-PAF) in ischaemic myocardium. 176 76

Most models of hypoxia and ischemia are used for evaluating the metabolic consequences of cerebral insult. They have also been used for inducing cognitive disturbance. The pathological cascade after severe hypoxia or ischemia includes decreased ATP, influx of Ca2+ and Na+ with decrease in intracellular K+ leading to depolarization, release of glutamate, noradrenaline and acetylcholine, changes in neuronal plasticity, cell death, and cognitive impairment. Possible pharmacological mechanisms for protecting brain function include blockade of Ca2+ influx, inhibition of cell swelling, regulation of membrane potential, inhibition of neurotransmitter release and inhibition of excitatory amino-acid receptors. Among the existing models, many suffer from poor reproducibility and standardization. Two models which are more satisfactory in this respect are global transient ischemia in gerbils induced by bilateral carotid occlusion and focal ischemia in rats induced by occlusion of the middle cerebral artery. Although clear protective effects have been observed in both kinds of model (e.g., with NMDA antagonists, Ca2+ antagonists, PAF antagonists) it is frequently difficult to extrapolate these effects to disorders associated with memory impairment.
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PMID:Models of hypoxia and cerebral ischemia. 218 22

The catastrophe theory evolved by Thom and Zeeman proposes a mathematical definition for the abrupt or 'catastrophic' changes that can suddenly occur in normally well-ordered and smooth-running systems. We have integrated this theory with our own PAF/cytokine feedback network hypothesis to explain the control and dysfunction of the inflammatory response. This process involves the activation of cells and factors such as proteases, and is coordinated by mediators such as PAF, cytokines and growth factors, minute amounts of which can prime cells to respond in an enhanced manner to subsequent agonistic stimuli. PAF and certain cytokines also possess the unique property of being able to induce the release of each other and their own generation in vivo. This 'singularity' may enable a self-generating feedback network to become established. The priming ability of these mediators indicates the extreme sensitivity of the inflammatory process and importance of a homeostatic equilibrium between the vectors involved in the priming and feedback processes and internal suppressive mechanisms. In pathological conditions, one can consider the phenomenon of PAF and cytokine autogeneration as a 'fold' in the feedback network and an expression of the singularity characteristic of the catastrophe hypothesis. This may lead to systemic toxicity and microcirculatory collapse, a characteristic feature of shock, sepsis, asthma, ischemia and graft rejection. A combination of drugs antagonizing the various feedback components may inhibit this catastrophic process and thus provide more successful therapy of these conditions.
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PMID:PAF/cytokine auto-generated feedback networks in microvascular immune injury: consequences in shock, ischemia and graft rejection. 251 89


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