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)

Disturbance of cerebral blood flow from causes such as meningitis, thromboembolic disease and atherosclerosis was considered an important factor in the pathogenesis of polioencephalomalacia in 25 dogs. In dogs with polioencephalomalacia of undetermined cause, the distribution of lesions in neocortex and paleocortex suggested a change of neuronal metabolism secondary to cerebral anoxia/ischemia. Five dogs with canine distemper infection had bilateral necrosis of the hippocampus and pyriform cortex. Convulsions, central visual impairment and hemiparesis were the most prominent neurologic signs.
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PMID:Polioencephalomalacia in the dog. 50 91

The author describes a family (48 year old mother and 15 year old son) with the muscular variant of glycogenosis-McArde's metabolic myopathy. The mother has been ill since 22 years old, the son--since 7. The disease had a slowly progressive development. The clinical picture was characterized by convulsions of the type of cramps following physical loadings on muscles of the body and extremities. Convulsions were accompanied by pain, an induration and enlargment of the muscles, muscle fatigue and increased significantly in an artifical ischemia of the extremities. A histochemical study of the muscle revealed a pathological accumulation of glycogen. The content of lactic and pyruvic acid in the blood after work in ischemic conditions did not change significantly. A study of the sugar curve in the blood with a loading with glucose and a parallel determination of insulin by a radioimmune method found hyperinsulinemia and a dysfunction of the pancreas.
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PMID:[McArdle's disease (a familial case)]. 106 64

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.
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PMID:Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. 109 Mar 93

A traumatic transection of the upper descending thoracic aorta, undiagnosed, was complicated on the tenth day by an acute obstruction of the descending thoracic aorta. The upper body hypertension resulted in generalised convulsions and cardiac failure with pulmonary oedema. The lower body ischemia resulted in paraplegia, acute ischemia of the lower limbs, liver failure and anuria. An emergency revascularisation of the lower body was achieved by axillary-bifemoral bypass. The improvement of the clinical status allowed complete repair of the aortic transection two days after the extra-anatomic revascularisation. This case emphasizes the severity of the cases with impaired blood flow to the lower body and the benefit of the extra-anatomic bypass in pathology of the upper descending thoracic aorta when complete repair of the aortic transection is associated with an extremely high risk.
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PMID:[Traumatic rupture of the aortic isthmus revealed by acute obstruction of the descending thoracic aorta]. 128 8

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

Regional cerebral blood flow (CBF) and regional cerebral glucose utilization (CGU) were studied by quantitative autoradiographic techniques in rats. Animals were treated either with a toxic dose of soman, an irreversible organophosphorus cholinesterase inhibitor, that produced convulsions or with saline as controls. An increased arterial blood pressure (mean increase = 41% of control) always preceded onset of convulsions. Convulsive activity was associated with an increase of plasma glucose concentration and marked increases over controls of CGU [average of all regions: control = 75 +/- 5 mumol.100 g-1.min-1, n = regions/animals (304/8); seizures = 451 +/- 20 mumol.100 g-1.min-1, n = 190/5] and CBF [average of all regions: control = 135 +/- 6 ml.100 g-1.min-1, n = 190/5; seizures = 619 +/- 29 ml.100 g-1.min-1, n = 190/5). Regional distribution of these effects revealed a greater proportional increase of CBF over CGU in cingulate, motor, and occipital cortex and caudate-putamen. In contrast, a lower proportional increase of CBF over CGU in CA3 region of hippocampus, dentate gyrus, medial thalamus, and substantia nigra was observed, implying the existence of a relative ischemia in these brain areas. These findings may be relevant to the pathogenesis of brain lesions associated with soman-induced convulsions.
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PMID:Cerebral blood flow and metabolism in soman-induced convulsions. 161 57

Platelet-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 genes fos and jun, whose gene products are regulators of the transcription of other genes. Transcription of fos 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 Ca(2+)-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.
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PMID: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. 166 21

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.
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PMID:Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders. 180 75

Antagonists for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor may have therapeutic potential as neuroprotectant agents in conditions of neuronal degeneration that include brain ischemia, Huntington's chorea, and Alzheimer's disease. Here we have investigated the pharmacological actions of LY274614, a structurally novel competitive NMDA receptor antagonist, for pharmacological selectivity and neuroprotectant effects following systemic administration. LY274614 potently displaced NMDA receptor ([3H]CGS19755) binding (IC50 = 58.8 +/- 10.3 nM), but had no appreciable affinity at [3H]AMPA or [3H]kainate receptor sites at up to 10,000 nM. NMDA-induced convulsions in neonatal rats or NMDA-induced lethality in mice are potently and selectively antagonized by i.p. or p.o. LY274614. Oral doses showed a delayed but prolonged duration of effect. In adult rats, the neurodegenerative effects (loss of choline acetyltransferase activity) following the intrastriatal infusions of NMDA or quinolinate, but not kainate, were prevented by LY274614 (2.5 to 20 mg/kg i.p.). LY274614 is an effective neuroprotectant agent against NMDA receptor-induced toxicity when administered systemically and is a promising therapeutic agent for conditions where glutamate plays a role in the pathology of neuronal degeneration.
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PMID:Neuroprotectant effects of LY274614, a structurally novel systemically active competitive NMDA receptor antagonist. 183 88

We have previously demonstrated that hypoxia is acutely epileptogenic in the immature rat but not in the adult. The window during which hypoxia induces seizures in the rat ranges from postnatal day (P) 5-17, with the most severe seizures occurring at P10-12. Perinatal hypoxia resulted in significantly more acute seizure activity than perinatal anoxia. The present study evaluates the long term effects of perinatal hypoxia versus anoxia. Animals were exposed to hypoxia (3%O2) or anoxia (0%O2) at P10 and challenged later in adulthood (P55-60) with administration of pentylenetetrazol (PTZ) (45 mg/kg subcutaneously). Compared to normal littermate controls, the animals which had been exposed to perinatal hypoxia had a significantly higher frequency of generalized convulsions (GC) and a significantly shorter latency to the first myoclonic jerk (MJ) after PTZ. In contrast, perinatal anoxia did not alter long term seizure susceptibility. These results are discussed in context of previous studies which have shown variable long term effects using different models of perinatal hypoxia and/or ischemia.
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PMID:Differential effects of perinatal hypoxia and anoxia on long term seizure susceptibility in the rat. 185 88


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