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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated production of hydrogen peroxide (H2O2) in the central nervous system has been implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, ischemic reperfusion, stroke, and Alzheimer's disease. Pyruvic acid has a critical role in energy metabolism and a capability to nonenzymatically decarboxylate H2O2 into H2O. This study examined the effects of glycolytic regulation of pyruvic acid on H2O2 toxicity in murine neuroblastoma cells. Glycolytic energy substrates including D-(+)-glucose, D-(-) fructose and the adenosine transport blocker dipyridamole, were not effective in providing protection against H2O2 toxicity, negating energy as a factor. On the other hand, pyruvic acid completely prevented H2O2 toxicity, restoring the loss of ATP and cell viability. H2O2 toxicity was also attenuated by D-fructose 1,6 diphosphate (FBP), phospho (enol) pyruvate (PEP), niacinamide, beta-nicotinamide adenine dinucleotide (beta-NAD+), and reduced form (beta-NADH). Both FBP and PEP exerted positive kinetic effects on pyruvate kinase (PK) activity. Interestingly, only pyruvic acid and beta-NADH exhibited powerful stoichiometric H2O2 antioxidant properties. Further, beta-NADH may exert positive effects on PK activity. Subsequent pyruvic acid accumulation can lead to the recycling of beta-NAD+ through lactate dehydrogenase and beta-NADH through glyceraldehyde-3-phosphate dehydrogenase. It was concluded from these studies that intracellular pyruvic acid and beta-NADH appear to act in concert through glycolysis, to enhance H2O2 intracellular antioxidant capacity in neuroblastoma cells. Future research will be required to examine whether similar effects are observed in primary neuronal culture or intact tissue.
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PMID:Cytoprotection of pyruvic acid and reduced beta-nicotinamide adenine dinucleotide against hydrogen peroxide toxicity in neuroblastoma cells. 1271 24

Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3-13C]pyruvate led to dose-dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3-13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4-13C]glutamate or [2-13C]GABA from [3-13C]pyruvate, but reduced formation of [4-13C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3-13C]lactate from [2-13C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo, but that care must be taken to avoid the seizure-inducing effect of pyruvate given in large doses.
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PMID:Brain metabolism of exogenous pyruvate. 1618 32

Oxidative stress is implicated in neurodegenerative diseases including stroke, Alzheimer's disease and Parkinson's disease, and has been extensively studied as a potential target for therapeutic intervention. Pyruvate, a natural metabolic intermediate and energy substrate, exerts antioxidant effects in brain and other tissues susceptible to oxidative stress. We tested the protective effects of pyruvate on hydrogen peroxide (H(2)O(2)) toxicity in human neuroblastoma SK-N-SH cells and the mechanisms underlying its protection. Hydrogen peroxide insult resulted in 85% cell death, but co-treatment with pyruvate dose-dependently attenuated cell death. At concentrations of >or=1 mM, pyruvate totally blocked the cytotoxic effects of H(2)O(2). Pyruvate exerted its protective effects even when its administration was delayed up to 2 h after H(2)O(2) insult. As a scavenger of reactive oxygen species (ROS), pyruvate dose-dependently attenuated H(2)O(2)-induced ROS formation, assessed from 2,7-dichlorofluorescein diacetate fluorescence. Furthermore, pyruvate suppressed superoxide production by submitochondrial particles, and attenuated oxidative stress-induced collapse of the mitochondrial membrane potential. Collectively, these results suggest that pyruvate protects neuronal cells through its antioxidant actions on mitochondria.
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PMID:Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells. 1717 85

The purpose of this study was to develop and validate a new tool to objectively quantify trunk orientation at the bedside, especially dedicated to the measurement of the lateropulsion in acute and subacute stroke patients. We developed software to analyze 2D movement with a CMOS camera (Logitech Quickcam Pro 4000) and to calculate the orientation of a segment defined by two color markers. First, the accuracy, reproducibility and noise when measuring segment orientations were evaluated with the CMOS camera placed in different positions, and second trunk orientation was measured in static and in dynamic conditions both with a CMOS camera and with a gold standard 3D video system (BTS SMART-e). Results showed that the measurement was accurate (mean error=0.05+/-0.12 degrees), reproducible (S.D. over five measurements=0.005 degrees ) and steady (noise signal=0.02 degrees ). The data obtained with the CMOS camera were highly correlated with those obtained with the 3D video system both in static and in dynamic conditions. However, the CMOS camera must be relatively well centered on the measured segment to avoid error due to image distortion. The parallax error was negligible. In conclusion, this could be an important step in the postural assessment of acute and subacute stroke patients. The CMOS camera, a simple, portable, compact, low-cost, commercially available apparatus is the first tool to objectively quantify lateropulsion at the bedside. This method could also support the development of a rehabilitation program for trunk orientation based on biofeedback using the real-time signal provided by the device.
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PMID:Measuring trunk orientation with a CMOS camera: feasibility and accuracy. 1725 46

We examined the tension responses to ramp shortening and lengthening over a range of velocities (0.1-5 L(0)/s) and at 20 degrees C and 30 degrees C in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L(0)) was 2.2 mm and sarcomere length approximately 2.5 microm. The tension change during ramp releases as well as ramp stretches showed an early transition (often appearing as an inflection) at 1-4 ms; the tension change at this transition and the length change at which it occurred increased with velocity. A second transition, indicated by a more gradual reduction in slope, occurred when the length had changed by 14-28 nm per half-sarcomere; the tension at this transition increased with lengthening velocity towards a plateau and it decreased with shortening velocity towards zero tension. The velocity dependence of the time to the transitions and the length change at the transitions showed some asymmetries between shortening and lengthening. Based on analyses of the velocity dependence of the tension and modelling, we propose that the first transition reflects the tension change associated with the crossbridge power stroke in shortening, or with the reversal of the power stroke in lengthening. Modelling shows that the reduction in slope at the second transition occurs when most of the crossbridges (myosin heads) that were attached at the start of the ramp become detached. After the second transition, the tension reaches a steady level in the model whereas the tension continues to increase during lengthening and continues to decrease during shortening in the experiments; this continuous tension change is seen at a wide range of initial sarcomere lengths and when active force is reduced by the myosin inhibitor, BTS. The continuous tension decline during shortening is not abolished by caffeine, but the rate of decline is reduced when the active force is depressed by BTS. We propose that stiffening of non-crossbridge visco-elastic elements upon activation contributes to the continuous tension rise during lengthening and the release of such tension and Ca-insensitive deactivation contribute to the tension decline during shortening in muscle fibres.
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PMID:Comparison of the tension responses to ramp shortening and lengthening in intact mammalian muscle fibres: crossbridge and non-crossbridge contributions. 1761 Jan 36

The removal of excess glutamate from brain fluids after acute insults such as closed head injury (CHI) and stroke is expected to prevent excitotoxicity and the ensuing long lasting neurological deficits. Since blood glutamate scavenging accelerates the removal of excess glutamate from brain into blood and causes neuroprotection, we have evaluated here whether the neuroprotective properties of pyruvate could be partly accounted to its blood glutamate scavenging activity. The neurological outcome of rats after CHI improved significantly when treated with intravenous pyruvate (0.9 mmoles/100 g) but not with pyruvate administered together with glutamate. Pyruvate, at 5 micromole/100 g rat was neither protective not able to decrease blood glutamate but displayed the latter two properties when combined with 60 microg/100 g of glutamate-pyruvate transaminase. Since the neurological recovery from CHI was correlated with the decrease of blood glutamate levels, we conclude that pyruvate blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms.
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PMID:The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury. 1808 Jan 87

Pyruvate, a key intermediate in glucose metabolism, was explored as a potential treatment in models of experimental stroke and inflammation. Pyruvate was administered to rodents after the onset of middle cerebral artery occlusion (MCAO). Since the extent of inflammation is often proportional to the size of the infarct, we also studied a group of animals given lipopolysaccharide (LPS) to cause brain inflammation without cell death. Following MCAO, pyruvate did not affect physiological parameters but significantly reduced infarct volume, improved behavioral tests and reduced numbers of neutrophils, microglial and NFkappaB activation. Animals given LPS showed increased microglial and NFkappaB activation which was almost completely abolished by pyruvate. Lactate, a major metabolite of pyruvate, was increased after pyruvate administration. However, administration of lactate itself did not have any anti-inflammatory effects. Pyruvate protects against ischemia possibly by blocking inflammation, but lactate itself does not appear to explain pyruvate's anti-inflammatory properties.
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PMID:Pyruvate protects against experimental stroke via an anti-inflammatory mechanism. 1963 62

Pyruvate is an important metabolic intermediate, and also is an effective scavenger of hydrogen peroxide and other reactive oxygen species (ROS). Pharmacological administration of pyruvate has been shown to improve organ function in animal models of oxidant-mediated cellular injury. However, pyruvate is relatively unstable in aqueous solutions, which could limit the therapeutic potential of this compound. Ethyl pyruvate (EP), a simple derivative of pyruvic acid, is also an ROS scavenger, but seems to exert pharmacological effects, such as suppression of inflammation, which are at least quantitatively different and in some instances are qualitatively distinct from those exerted by pyruvate anion. Treatment with EP has been shown to improve survival and/or ameliorate organ dysfunction in a wide variety of pre-clinical models of acute illnesses, such as severe sepsis, acute pancreatitis and stroke. Using other animal models, some studies have demonstrated that more prolonged treatment with EP can ameliorate inflammatory bowel disease or slow the rate of growth of malignant tumors. In a clinical trial of patients undergoing cardiac surgery, treatment with EP was shown to be safe, but it failed to improve outcome. The true therapeutic potential of EP and related compounds remains to be elucidated. In this review, some of the biochemical mechanisms, which might be responsible for the pharmacological effects of EP, are discussed.
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PMID:The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. 2023 Aug

Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to elucidate metabolic effects of pyruvate treatment on cybrid human 143B osteosarcoma cells harboring normal (2SA) and MELAS mutant (2SD) mitochondria. The results demonstrated dramatic and sustainable effects of pyruvate administration on the energy metabolism of 2SD cells, corroborating pyruvate as a metabolically rational treatment regimen for improving symptoms associated with MELAS and possibly other mitochondrial diseases.
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PMID:Metabolomic profiling rationalized pyruvate efficacy in cybrid cells harboring MELAS mitochondrial DNA mutations. 2288 39

The aim of this study was to present kinematics of trunk and upper extremities in tennis players who perform one-handed and two-handed backhand strokes. The study aimed to address the question of whether one of those techniques has some important advantage over the other. If so, what makes it superior? The study included 10 tennis coaches with average coaching experience of 9 years. The coaches were asked to hit 15 one-handed and two-handed backhands. The tests were carried out in a laboratory. A sponge ball was used in order to protect the measurement equipment. Video motion analysis was carried out using BTS SMART system; images were recorded with 6 cameras with a rate of 120 frames per second. The analysis of both backhand strokes focused on the second phase of the stroke (acceleration). The use of an eight-element model of human body for description of upper body motion in both techniques revealed kinematic differences in how both backhands are performed. The two-handed backhand was performed in closed kinetic chain with 8 degrees of freedom, whereas the one-handed backhand involved an open kinetic chain with 7 degrees of freedom. Higher rigidity of upper extremities which are connected with trunk in the two-handed backhand, contributes to an elevated trunk effect in this stroke. This is confirmed by higher component velocities for racket handle, which result from trunk rotation in the two-handed backhand and a negative separation angle in the two-handed backhand at the moment of contact of the racket with the ball. The study does not provide a clear-cut answer to the question of advantages of one technique over the other; however, it reveals dissimilar patterns of driving the racket in both techniques, which suggests the need for extending the analysis of techniques of both backhands with additional kinematics of tennis racket in consideration of measurements of ball velocities.
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PMID:The kinematics of trunk and upper extremities in one-handed and two-handed backhand stroke. 2348 50


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