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)

Normal pressure glaucoma (NPG) is a heterogeneous pathology of the optic nerve and retina. Besides, primary open-angle glaucoma (POAG) with high pressure belongs equally to the heterogeneous group. The risk factors and pathogenesis stages of NPG and those of POAG do not coincide completely. A considerable number of the NPG cases can be attributed to the glaucoma of pseudo-normal pressure. The individual norm of the intraocular pressure (IOP) does not coincide with the statistical standards. At the same time, POAG with high pressure has, to a more or less extent, the specific features peculiar to NPG. This is especially characteristic of POAG with moderately high IOP. The NPG specific features peculiar to a majority of the examined patients were related with an insufficient cerebral blood circulation caused by occlusive processes in the great and small vessels of the brain, by the nature of the collateral blood circulation and by a dysfunction of the vascular endothelium due to an exhaustion of the cerebral perfusion reserve. The latter is formed mainly at the cost of the vertrebobasilar basin. The mentioned basin supplies blood to the visual tract, as well as to the cerebral centers of the visual analyzer and of the midbrain. Ischemia of the upper corpus bigeminum and of the optic nucleus of the corpus geniculate laterale reduces the formation and supply of neurotrophines (in particular, of BNDF) with the axonal transport to the retinal ganglionic cells, which leads to their apoptosis. Cavernous dystrophy of the optic nerve is a factor preconditioning the occurrence of excavation of the optic nerve head. The mechanic factor related with excavation cannot be ruled out, either. NPG patients often have a relatively large size of the optic nerve disk (OND), therefore, their disk area is equally large. The pressure exerted on the OND is proportional not only to an IOP value, it is also proportional to a disk area. Consequently, provided the IOPs are identical, the mechanical forces exerted on the OND would differ with direct dependence on a disk area. There is every reason to suggest that a considerable share of NPG cases are preconditioned by the cerebrovascular pathology and, therefore, not only the ophthalmologist but also the neurologist must be involved in the diagnostics and treatment of such patients.
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PMID:[Normal-pressure glaucoma: a hypothesis of pathogenesis]. 1367 95

The sensitivity of different excitatory and inhibitory segmental reflex pathways to ischemia was investigated by monosynaptic reflex testing in the spinal cat. Spinal cord ischemia was established by aortal snare occlusion of 1-10 min duration. Excitatory and inhibitory spinal pathways showed statistically significant different susceptibility to ischemic impact. In the period of decreasing responses after the onset of ischemia the transmission through oligo- or polysynaptic, facilitatory or inhibitory pathways was found to be depressed earlier than that of monosynaptic pathways. The period from the end of ischemia until the beginning of recovery of reflex effects was significantly longer for inhibitory effects, compared to the monosynaptic reflexes alone.The results indicated that interneurones of excitatory segmental pathways may be less sensitive to ischemia than motoneurones, and motoneurones seem to be less sensitive to ischemia than interneurones of inhibitory pathways. In high spinal animals, with a relatively high level of extensor inhibition, the enhanced excitability of inhibitory interneurones to GS motoneurones may be responsible for their sensitivity to ischemia, due to an increased rate of O(2) consumption and exhaustion of high-energy phosphate resources.
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PMID:Different susceptibility of facilitatory and inhibitory spinal pathways to ischemia in the cat. 1456 18

Following metabolic size allometry, the specific metabolic rate of mammals increases with decreasing body mass, resulting in a steeper metabolic fall-off and a faster exhaustion of energy reserves under hypoxic conditions. However, both mammalian hibernators and fetuses are able to temporarily "switch-off" Kleiber's rule as an adaptation to limited food or oxygen supply. Further exceptions to the usual metabolic size relationship are observed in newborn mammals. For instance, neonatal mouse hearts exhibit slower calorimetric "dying curves" under conditions of ischemia, although their aerobic tissue metabolic rates are higher than in adult samples. This is apparently due to a transient reduction of metabolic rate back to the former feto-maternal level. A continuing deviation from metabolic size allometry is found in newborn marsupials (Monodelphis domestica) where the "inappropriately" low specific metabolic rate is a precondition of efficient growth and tissue aerobiosis in spite of extreme immaturity. Obviously, adaptive suppression of elevated metabolism in organisms of small size results in a dramatic improvement of oxygen supply. Vice-versa, the overall increase in specific metabolic rate with decreasing body size might be regarded as one of several phylogenetic adaptations to protect tissues from hyperoxygenation.
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PMID:Metabolic adaptation to hypoxia: cost and benefit of being small. 1528 95

Ischemic bowel disease exhibits a complex spectrum of clinical presentations and in the athlete the disease may be superimposed on dehydration, hyperthermia, and exhaustion. Physicians caring for athletes should be aware of the manifestations of ischemic bowel disease and the optimum methods of diagnosis and treatment. Abdominal pain and diarrhea are typical initial symptoms of ischemia and these symptoms generally limit further damage. However, symptoms may be overridden in cases of extreme athletic competition or other significant endurance events such as combat. Athletes and coaches should be aware of the danger of ischemic bowel disease. Patients or athletes with recurrent symptoms of abdominal pain and diarrhea during exercise may be at increased risk for ischemic damage. However, no underlying anatomic abnormalities have been noted. Ischemic hemorrhagic gastritis is generally reversible and may be controlled with effective acid blockade. Ischemic colitis generally presents with pain, diarrhea, and bleeding. It is usually mild but may require volume and transfusion support, rarely progressing to need for resection or stricture. Severe presentations with intestinal infarction are rare but potentially life threatening. The athlete is usually able to ultimately resume his or her activities without restriction.
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PMID:Exercise-associated intestinal ischemia. 1576 45

Astrocytes are multifunctional cells that interact with neurons and other astrocytes in signaling and metabolic functions, and their resistance to pathophysiological conditions can help restrict loss of tissue after an ischemic event provided adequate nutrients are supplied to support their requirements. Astrocytes have substantial oxidative capacity and mechanisms to upregulate glycolytic capability when respiration is impaired. An astrocytic enzyme that synthesizes a powerful activator of glycolysis is not present in neurons, endowing astrocytes with the ability to sustain ATP production under restrictive conditions. The monocarboxylic acid transporter (MCT) isoforms predominating in astrocytes are optimized to facilitate very large increases in lactate flux as lactate concentration increases within (1-3 mM) and above (>3 mM) the normal range. In sharp contrast, the major neuronal MCT serves as a barrier to increased transmembrane transport as lactate rises above 1 mM, restricting both entry and efflux. Lactate can serve as fuel during recovery from ischemia but direct evidence that lactate is oxidized by neurons (vs. astrocytes) to maintain synaptic function is lacking. Astrocytes have critical roles in regulation of ionic homeostasis and control of extracellular glutamate levels, and spreading depression associated with ischemia places high demands on energy supplies in astrocytes and contributes to metabolic exhaustion and demise. Disruption of Ca2+ homeostasis, generation of oxygen free radicals and nitric oxide, and mitochondrial depolarization contribute to astrocyte death during and after a metabolic insult. Novel pharmaceutical agents targeted to astrocytes and hyperoxic therapy that restores penumbral oxygen level during energy failure might improve postischemic outcome.
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PMID:Astrocytic contributions to bioenergetics of cerebral ischemia. 1584 8

Cold storage of the whole liver at 4 degrees C in SBS and UW solution allowed to prevent from osmotic swelling of cells, which appeared at early stages of liver storage at 4 degrees C in just saline solutions. This effect of preserving solutions contributes to the preservation of quite high level of intracellular ATP content in liver at the first two stages of hypothermic storage (6 and 18 hrs), which preserves even during following normothermic reperfusion of an organ. A statistical ATP reduction in comparison with the control level (almost twice) can be explained on the one hand by the exhaustion of intracellular substrates of oxidation and on the other hand by their loss for the supporting of homeostasis under cold ischemia and following incubation of liver at 37 degrees C.
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PMID:[ATP level in the whole rat liver during cold hypoxia and subsequent rewarming]. 1590 29

ClC proteins are a family of chloride channels and transporters that are found in a wide variety of prokaryotic and eukaryotic cell types. The mammalian voltage-gated chloride channel ClC-1 is important for controlling the electrical excitability of skeletal muscle. Reduced excitability of muscle cells during metabolic stress can protect cells from metabolic exhaustion and is thought to be a major factor in fatigue. Here we identify a novel mechanism linking excitability to metabolic state by showing that ClC-1 channels are modulated by ATP. The high concentration of ATP in resting muscle effectively inhibits ClC-1 activity by shifting the voltage gating to more positive potentials. ADP and AMP had similar effects to ATP, but IMP had no effect, indicating that the inhibition of ClC-1 would only be relieved under anaerobic conditions such as intense muscle activity or ischemia, when depleted ATP accumulates as IMP. The resulting increase in ClC-1 activity under these conditions would reduce muscle excitability, thus contributing to fatigue. We show further that the modulation by ATP is mediated by cystathionine beta-synthase-related domains in the cytoplasmic C terminus of ClC-1. This defines a function for these domains as gating-modulatory domains sensitive to intracellular ligands, such as nucleotides, a function that is likely to be conserved in other ClC proteins.
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PMID:Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels. 1602 67

During exercises with relatively small muscle masses, limitations to exercise performance by the cardiovascular system should be significantly reduced, allowing one to fully-test the "oxidative potential" of the investigated muscles. Ten elderly males (E, 77.8 +/- 2.9 years [x +/- SD]) and eight young controls (Y, 26.6 +/- 3.0) underwent incremental exercises to voluntary exhaustion on a dynamic leg-extension (dominant limb) machine (knee-extension, KE) and on a cycloergometer (CYCLO). During KE the load was increased every 3 min to loads corresponding to 20, 40 and 60% of the force of one-repetition maximum (1RM). The following variables were determined (vastus lateralis muscle): concentration changes of deoxygenated haemoglobin and myoglobin (Delta[deoxy(Hb + Mb)]) by near-infrared spectroscopy (NIRS), expressed as percentage of the maximal value obtained during transient limb ischemia, and taken as an index of O2 extraction; root mean square (RMS) and median power frequency (MDF) by electromyography. The total lifted load during KE and peak workload during CYCLO were lower in E versus Y (620.4 +/- 321.9 kg vs. 1347.4 +/- 458.7; 113.5 +/- 23.9 W vs. 224.3 +/- 41.0, respectively). During CYCLO Delta[deoxy(Hb + Mb)] peak (i.e. the value determined at exhaustion) was lower in E (44.5 +/- 17.7%) versus Y (67.1 +/- 22.9), whereas during KE Delta[deoxy(Hb + Mb)] peak was higher in E (56.8 +/- 20.9%) versus Y (38.6 +/- 15.8). "Thresholds", that is abrupt increases in RMS slopes, were detected in Y but not in E, suggesting less recruitment or a preferential atrophy of type 2 fibers in the elderly. These findings, associated with the preserved capacity of O2 extraction, suggest a shift towards oxidative metabolism in skeletal muscles of 78 year-old subjects, which could preserve, at least in part, their capacity to carry out exercise.
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PMID:Insights into central and peripheral factors affecting the "oxidative performance" of skeletal muscle in aging. 1718 97

Alterations in myocardial glucose metabolism are a key determinant of ischemia-induced depression of left ventricular mechanical function. Since myocardial glycogen is an important source of endogenous glucose, we compared the effects of ischemia on glucose uptake and utilization in isolated working rat hearts in which glycogen content was either replete (G replete, 114 micromol/g dry wt) or partially depleted (G depleted, 71 mumol/g dry wt). The effects of low-flow ischemia (LFI, 0.5 ml/min) on glucose uptake, glycogen turnover (glycogenolysis and glycogen synthesis), glycolysis, adenosine 5'-monophosphate-activated protein kinase (AMPK) activity, and GLUT4 translocation were measured. Relative to preischemic values, LFI caused a time-dependent reduction in glycogen content in both G-replete and G-depleted groups due to an acceleration of glycogenolysis (by 12-fold and 6-fold, respectively). In G-replete hearts, LFI (15 min) decreased glucose uptake (by 59%) and did not affect GLUT4 translocation. In G-depleted hearts, LFI also decreased initially glucose uptake (by 90%) and glycogen synthesis, but after 15 min, when glycogenolysis slowed due to exhaustion of glycogen content, glucose uptake increased (by 31%) in association with an increase in GLUT4 translocation. After 60 min of LFI, glucose uptake, glycogenolysis, and glycolysis recovered to near-preischemic values in both groups. LFI increased AMPK activity in a time-dependent manner in both groups (by 6-fold and 4-fold, respectively). Thus, when glycogen stores are replete before ischemia, ischemia-induced AMPK activation is not sufficient to increase glucose uptake. Under these conditions, an acceleration of glycogen degradation provides sufficient endogenous substrate for glycolysis during ischemia.
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PMID:Ischemia-induced activation of AMPK does not increase glucose uptake in glycogen-replete isolated working rat hearts. 1817 21

Uric acid (UA) is the end product of purine catabolism in humans and is a powerful antioxidant whose generation is increased under ischemic conditions. However, both clinical and experimental studies reveal a gradual exhaustion of the antioxidant capacity after transient cerebral ischemia, and the magnitude of this consumption seems to be correlated with the extent of brain tissue injury, growth of the infarction, severity of neurological impairment in the acute phase, and long-term functional outcome. Growing evidence supports the neuroprotective effect of UA administration after brain ischemia. In experimental conditions, the administration of UA is neuroprotective both in mechanical models of brain ischemia (transient or permanent intraluminal occlusion of the middle cerebral artery) and in thromboembolic models of autologous clot injection. The administration of UA is feasible and safe in healthy volunteers. In acute stroke patients treated with recombinant tissue plasminogen activator (rt-PA), co-administration of UA has proven to reduce lipid peroxidation and to prevent the fall in UA blood levels that occur very early after stroke onset. Currently, a multicentric Phase III clinical trial is testing whether the administration of UA increases the clinical benefits of rt-PA, which represents the only approved therapy in patients with acute ischemic stroke. This review summarizes the available information justifying such a novel therapeutic approach in this devastating clinical condition.
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PMID:Uric acid administration in patients with acute stroke: a novel approach to neuroprotection. 1827 11


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