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)

A case of parkinsonian syndrome caused by normal pressure hydrocephalus (NPH) accompanied by cauda equina neurinoma is reported. A 69-year-old woman presented with typical symptoms of parkinsonism, including akinesia, resting and postual tremor, and cog-wheel rigidity. CT scan of the brain revealed dilatation of ventricles, but she did not present dementia and urinary incontinence that are common symptoms in NPH. Her cerebrospinal fluid (CSF) pressure was normal, and her protein level was high at 2,970 mg/dl. An electroencephalogram (EEG) showed diffuse slow waves. An IMP-SPECT images of the brain showed diffuse reduction of radioisotope uptake. Levodopa was not effective in treating her parkinsonism. Removal of the tumor caused dramatic improvement in her parkinsonism. Her CSF protein level was normalized and EEG and SPECT images were improved after the operation. However, ventricular size on brain CT showed no change. It was considered that the causal mechanism of NPH was due to high protein levels in the CSF. The parkinsonism in this case was caused by dysfunction of the circuits linking the cortex, basal ganglia, and thalamus associated with metabolic disorder due to periventricular ischemia. Typical parkinsonism caused by NPH associated with spinal cord tumor has not been reported. When we examine a patient with parkinsonian syndrome caused by NPH, we should check the CSF protein level. And if that level is high, the possibility of spinal cord tumor should be considered.
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PMID:[A case of parkinsonian syndrome caused by normal pressure hydrocephalus accompanied by the cauda equina neurinoma]. 1242 62

Myocardial and endothelial damage is still a widely debated problem during the ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine metabolites, antioxidant defense mechanisms, oxidative status and endothelial dysfunction markers in 14 patients undergoing coronary artery by-pass graft (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue were analyzed for glutathione, NAD, nucleotide nucleoside and base content by capillary electrophoresis (CE). In plasma samples from the coronary sinus we evaluated: nitrate and nitrite concentrations by CE, plasma glutathione peroxidase (plGPx) by ELISA, endothelin-1 (ET-1) by RIA and reactive oxygen metabolites (ROM) by colorimetric assay. During the ischemic period (t2) we observed a reduction in cellular NAD and GSH levels, as well as nitrate, nitrite and plGPx. ATP and GTP levels decreased and their catabolic products AMP, GMP, IMP, adenosine, inosine and hypoxanthine accumulated. The energy charge, ATP/ADP ratio, and nucleotide/(nucleoside + base) ratios decreased. At t3, levels of plasma ET-1 increased and monophosphate nucleotides tended to return to basal values. The energy charge did not increase but the nucleotide/(nucleoside + nucleobase) ratio recovered to some extent. Levels of nitrates plus nitrites continued to decrease. No significant variation in ROM levels was observed. Our data indicate that oxidative stress and endothelial damage are major events during CABG, overwhelming the scavenging capacity of the myocyte and preventing restoration of the normal energy balance for 30 min after reperfusion. The AMP deaminase pathway leading to IMP production is active during ischemia and adenosine is not the main compound derived from ATP break-down in the human heart. The possible role of extracorporeal circulation is also discussed.
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PMID:Cardiac surgery: myocardial energy balance, antioxidant status and endothelial function after ischemia-reperfusion. 1250 69

We report a case of dural arteriovenous fistula of the anterior cranial fossa with venous ischemia. A 55-year-old man presented with headache and visual disturbance. Neurological examination showed no abnormality. MR images demonstrated flow void at the right anterior cranial fossa. Right internal carotid angiograms showed a dural arteriovenous fistula of the anterior cranial fossa, fed by the anterior ethmoidal artery. The draining vein was the leptomeningeal vein draining into the basal vein, the straight sinus, and the left transverse sinus. 123I-IMP SPECT revealed a low perfusion area in the left occipital region. We interrupted the draining vein at the anterior cranial fossa. Angiographic cure was obtained and venous circulation was improved. 123I-IMP SPECT revealed improvement in the low perfusion area in the left occipital region. The postoperative course was uneventful. We discuss the clinical features, the hemodynamic findings and the management of this case.
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PMID:[The improvement in regional cerebral blood flow in the anterior cranial fossa which was affected by a dural arteriovenous fistula: case report]. 1261 58

It has been reported that the xanthine oxidase inhibitor, allopurinol, has a protective effect on ischemia - reperfusion injury, but the precise mechanism of its action is still unclear. Therefore, in the present study the mechanisms of the myocardial protection of allopurinol were evaluated in isolated perfused rat hearts. Allopurinol significantly inhibited myocardial xanthine oxidase activity, and improved left ventricular dysfunction after ischemia - reperfusion. In addition, the lactate dehydrogenase content in the coronary effluent obtained after reperfusion was significantly decreased. ATP, ADP, AMP and IMP significantly decreased, whereas inosine, hypoxanthine and xanthine significantly increased after ischemia in both the control and allopurinol groups. The concentration of xanthine was significantly decreased after ischemia - reperfusion in the allopurinol group; however, allopurinol did not affect the other purine metabolites. To evaluate the accumulation of oxidative stress, thiobarbituric acid reactive substances (TBARS) production in myocardial tissue was measured and allopurinol significantly decreased TBARS formation after ischemia - reperfusion. Finally, myocardial hydroxyl radicals were directly measured by electron spin resonance spectroscopy with the nitroxide radical 4-hydroxy-2, 2,6,6-tetramethyl-piperidine-N-oxyl. Hydroxyl radicals significantly increased immediately after reperfusion, but were significantly decreased in the allopurinol group. In conclusion, allopurinol reduced myocardial injury after ischemia-reperfusion by suppressing oxidative stress, but not by salvage of ATP. These findings may lead to the development of new therapeutic strategies for myocardial ischemia - reperfusion injury.
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PMID:Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts. 1293 55

Impaired tolerance to ischemia-reperfusion in older hearts may stem in part from alterations in purine catabolism, impacting on maintenance of energy state and protective signaling via extracellular adenosine. We characterized effects of aging on normoxic and post-ischemic purine metabolism in hearts from young (2-4 month), middle-aged (12 month), old (18 month), and senescent (24-28 month) C57/Bl6 mice. Normoxic function was similar in all age groups while normoxic purine efflux increased gradually with age. This was the result of enhanced efflux of hypoxanthine, xanthine and uric acid, with extracellular accumulation of adenosine and inosine remaining unchanged. While total purine washout during 60 min reperfusion following 20 min global ischemia was unaltered by aging (1057+/-109 nmoles/g in young vs. 1221+/-127 nmoles/g in senescent hearts), selective changes in purine catabolism were evident. Accumulation of adenosine and inosine were reduced by 50 and 80%, respectively, matched by 400 and 300% elevations in hypoxanthine and xanthine accumulation, respectively. Uric acid remained unchanged. Thus, while adenosine and inosine represented 15+/-2 and 47+/-3% of total purine efflux in young hearts, these values decreased to only 6+/-1 and 9+/-2% in senescent hearts. Efflux of IMP also increased 500% with aging whereas 5'-AMP was unaltered. These changes were associated with a substantial fall in ischemic tolerance, with left ventricular developed pressure recovering to 46+/-3% in young hearts vs. only 24+/-6, 16+/-4, and 19+/-4% in middle-age, old and senescent hearts, respectively. Our data collectively support a pronounced shift in purine catabolism, with reduced accumulation of salvageable and cardioprotective adenosine, and enhanced accumulation of poorly salvaged (and potentially injurious) hypoxanthine and xanthine. Mechanisms underlying this shift have yet to be determined. However, this may play a role in the marked decline in myocardial tolerance to ischemia with aging and senescence.
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PMID:Aging-related changes in myocardial purine metabolism and ischemic tolerance. 1458 Aug 70

Brief hypoxia or ischemia perturbs energy metabolism inducing paradoxically a stress-tolerant state, yet metabolic signals that trigger cytoprotection remain poorly understood. To evaluate bioenergetic rearrangements, control and hypoxic hearts were analyzed with 18O-assisted 31P NMR and 1H NMR spectroscopy. The 18O-induced isotope shift in the 31P NMR spectrum of CrP, betaADP and betaATP was used to quantify phosphotransfer fluxes through creatine kinase and adenylate kinase. This analysis was supplemented with determination of energetically relevant metabolites in the phosphomonoester (PME) region of 31P NMR spectra, and in both aromatic and aliphatic regions of 1H NMR spectra. In control conditions, creatine kinase was the major phosphotransfer pathway processing high-energy phosphoryls between sites of ATP consumption and ATP production. In hypoxia, creatine kinase flux was dramatically reduced with a compensatory increase in adenylate kinase flux, which supported heart energetics by regenerating and transferring beta- and gamma-phosphoryls of ATP. Activation of adenylate kinase led to a build-up of AMP, IMP and adenosine, molecules involved in cardioprotective signaling. 31P and 1H NMR spectral analysis further revealed NADH and H+ scavenging by alpha-glycerophosphate dehydrogenase (alphaGPDH) and lactate dehydrogenase contributing to maintained glycolysis under hypoxia. Hypoxia-induced accumulation of alpha-glycerophosphate and nucleoside 5'-monophosphates, through alphaGPDH and adenylate kinase reactions, respectively, was mapped within the increased PME signal in the 31P NMR spectrum. Thus, 18O-assisted 31P NMR combined with 1H NMR provide a powerful approach in capturing rearrangements in cardiac bioenergetics, and associated metabolic signaling that underlie the cardiac adaptive response to stress.
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PMID:Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy. 1497 88

ATP concentration is dramatically affected in ischemic injury. From previous studies on ATP mediated purine and pyrimidine salvage in CNS, we observed that when "post-mitochondrial" extracts of rat brain were incubated with ATP at 3.6 mM, a normoxic concentration, formation of IMP always preceded that of adenosine, a well known neuroactive nucleoside and a homeostatic cellular modulator. This observation prompted us to undertake a study aimed at assessing the precise pathways and kinetics of ATP breakdown, a process considered to be the major source of adenosine in rat brain. The results obtained using post-mitochondrial extracts strongly suggest that the breakdown of intracellular ATP at normoxic concentration follows almost exclusively the pathway ATP<=>ADP<=>AMP --> IMP --> inosine<=>hypoxanthine, with little, if any, intracellular adenosine production. At low ischemic concentration, intracellular ATP breakdown follows the pathway ATP<=>ADP<=>AMP --> adenosine --> inosine<=>hypoxanthine with little IMP formation. At the same time, extracellular ATP, whose concentration is known to be enhanced during ischemia, is actively broken down to adenosine through the pathway ATP --> ADP --> AMP --> adenosine, catalysed by the well characterized ecto-enzyme cascade system. Moreover, we show that during intracellular GTP catabolism, xanthosine, in addition to guanosine, is generated through the so called "ribose 1-phosphate recycling for nucleoside interconversion". These results considerably extend our knowledge on the long debated question of the extra or intracellular origin of adenosine in CNS, suggesting that at least in normoxic conditions, intracellular adenosine is of extracellular origin.
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PMID:Metabolic regulation of ATP breakdown and of adenosine production in rat brain extracts. 1531 67

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

Mechanisms of adenosine (ADO) protection of reperfused myocardium are not fully understood. We tested the hypothesis that ADO (0.1 mM) alleviates ventricular stunning by ADO A(1)-receptor stimulation combined with purine metabolic enhancements. Langendorff guinea pig hearts were stunned at constant left ventricular end-diastolic pressure by low-flow ischemia. Myocardial phosphate metabolites were measured by (31)P-NMR, with phosphorylation potential {[ATP]/([ADP].[P(i)]), where brackets indicate concentration} estimated from creatine kinase equilibrium. Creatine and IMP, glycolytic intermediates, were measured enzymatically and glycolytic flux and extracellular spaces were measured by radiotracers. All treatment interventions started after a 10-min normoxic stabilization period. At 30 min reperfusion, ventricular contractility (dP/dt, left ventricular pressure) was reduced 17-26%, ventricular power (rate-pressure product) by 37%, and [ATP]/([ADP].[P(i)]) by 53%. The selective A(1) agonist 2-chloro-N(6)-cyclo-pentyladenosine marginally preserved [ATP]/([ADP].[P(i)]) and ventricular contractility but not rate-pressure product. Purine salvage precursor inosine (0.1 mM) substantially raised [ATP]/([ADP].[P(i)]) but weakly affected contractility. The ATP-sensitive potassium channel blocker glibenclamide (50 microM) abolished ADO protection of [ATP]/([ADP].[P(i)]) and contractility. ADO raised myocardial IMP and glucose-6-phosphate, demonstrating increased purine salvage and pentose phosphate pathway flux potential. Coronary hyperemia alone (papaverine) was not cardioprotective. We found that ADO protected energy metabolism and contractility in stunned myocardium more effectively than both the A(1)-receptor agonist 2-chloro-N(6)-cyclo-pentyladenosine and the purine salvage precursor inosine. Because ADO failed to stimulate glycolytic flux, the enhancement of reperfusion, [ATP]/([ADP].[P(i)]), indicates protection of mitochondrial function. Reduced ventricular dysfunction at enhanced [ATP]/([ADP].[P(i)]) argues against opening of mitochondrial ATP-sensitive potassium channel. The results establish a multifactorial mechanism of ADO antistunning, which appears to combine ADO A(1)-receptor signaling with metabolic adenylate and antioxidant enhancements.
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PMID:Adenosine enhances cytosolic phosphorylation potential and ventricular contractility in stunned guinea pig heart: receptor-mediated and metabolic protection. 1734 37

Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). Seizure is known as a rare complication after revascularization for moyamoya disease, although its underlying mechanism is undetermined. We investigated the relationship between seizure attack and postoperative alteration in CBF in patients with moyamoya disease. CBF was routinely measured by N-isopropyl-p-[123I] iodpamphetamine (123I-IMP-SPECT) 1 and 7 days after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis on 64 sides of the 44 consecutive patients (male:female = 13:31, 2-62 years old) with moyamoya disease. Three patients (male:female = 1:2, 40-55 years old) suffered from seizure attack at 1 to 10 days after surgery. Two of the three patients manifested as seizures at 8-10 days after surgery and presented transient neurologic deteriolation before seizure. Postoperative SPECT revealed significant increase in CBF at the sites of the anastomosis in all three patients. Postoperative magnetic resonance imaging showed no ischemic changes, and magnetic resonance angiography showed the apparently patent STA-MCA anastomosis as thick high signal intensity sign in all three patients. The anatomical location and the temporal profile of hyperperfusion were completely in accordance with the focus of seizure attack. Intensive blood pressure control and the use of antiepileptic agents were instituted. The neurologic deficits were resolved and no seizure attack recurred in three patients. Seizure following STA-MCA anastomosis can be caused by hyperperfusion in patients with moyamoya disease. When seizure attacks occur, routine CBF measurement is recommended to differentiate hyperperfusion and ischemia, since the treatments for these conditions are contradictory.
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PMID:[Seizure following superficial temporal-middle cerebral artery anastomosis in patients with moyamoya disease: possible contribution of postoperative cerebral hyperperfusion]. 1749 42


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