Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male, pathogen-free Fischer 344 rats aged 6 and 24 mo were exposed to 1.5 or 3.0 ppm for 8 h and recovery rates of diphosphonucleotides (NAD+ and NADH) and triphosphonucleotides (NADP+ and NADPH) were measured and compared to controls. Recovery after 0.5 ppm was not examined because no significant changes occurred in either age group after this lower exposure. At zero time (immediately after exposures) both concentrations are depressed in adults and aged animals except for NADH in aged animals at 3.0 ppm; NADP+ in adults at 1.5 and 3.0 ppm was decreased, but not significantly. For NAD+ and NADH, recovery of whole lung concentrations is complete by 24 h following an 8-h exposure to 1.5 or 3.0 ppm of ozone. Only after 3.0 ppm of ozone was the ratio of the reduced to oxidized form (NADH/NAD+) still elevated after 24 h; however, it also returned to control levels by 96 h. For the triphosphonucleotides, an 8-h exposure to 1.5 ppm of ozone resulted in a sustained depression of whole lung concentrations of NADPH throughout the 96-h recovery period. Also, only after the 1.5 ppm exposure was the reduced to oxidized ratio (NADPH/NADP+) significantly depressed throughout the 96-h recovery period. Unexpectedly, recovery of whole lung levels returned to normal within 24 h after the 8-h exposure to both the 1.5 and the 3.0 ppm concentrations. With the exception of the sustained effect on NADPH levels, these data indicate that di- and triphosphonucleotide concentrations rapidly return to normal in the lung after severe, acute oxidant injury. There were no differences in recovery rates between the adult and the aged groups.
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PMID:Recovery of lung pyridine nucleotides following acute exposure of adult and aged rats to ozone. 183 64

We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.
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PMID:Cerebral blood flow and oxygen consumption in cortical spreading depression. 187 15

Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH (nicotine adenine dinucleotide) redox state from rat brain during three- or four-vessel occlusion. To compare the completeness of the electrocauterization of the vertebral arteries and the effectiveness of the anterior cerebral arteries, two light guides were implanted above the cerebral hemispheres. The NADH level was measured and correlated with the changes in the intensity of the reflected light at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In the present study, we used ten rats in which unilateral and bilateral carotid occlusion were performed. In a second group of rats we tested the effects of four-vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as compared with those recorded under spreading depression conditions. These experiments were done by using the multiprobe assembly (MPA) approach. The results could be summarized as follows: (1) in the four-vessel occlusion model, the level of cerebral ischaemia could be estimated quantitatively, in real-time, by monitoring the NADH redox state; (2) unilateral carotid occlusion (after vertebral coagulation) led to a variable level of ipsilateral ischaemia, depending upon the blood flow compensation between the two hemispheres; (3) fibre-optic fluorometry enabled the correlation of NADH redox state with other physiological parameters as well as during after-brain ischaemia; (4) using the MPA in rats exposed to four-vessel occlusion as well as spreading depression, we identified the differences between the two pathological states, although there were some similarities in the ion homeostasis responses.
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PMID:Brain mitochondrial redox state, tissue haemodynamic and extracellular ion responses to four-vessel occlusion and spreading depression in the rat. 198 68

1. The carotid body chemoreceptors are stimulated in situ by hypoxia. We have studied type I cells freshly dissociated from the carotid body of the rabbit. We have used microfluorimetric and patch clamp techniques to examine the responses to hypoxia, to anoxia, and to metabolic inhibition. 2. NADH autofluorescence measured at both 400 and 500 nm increased rapidly and reversibly in response to anoxia or to cyanide (CN-), reflecting a change in mitochondrial metabolism. 3. Indo-1 was used to measure changes in intracellular calcium, [Ca2+]i. Anoxia reversibly increased [Ca2+]i from approximately 50-100 to approximately 200-450 nM in all cells tested. The response showed a striking temperature sensitivity. Responses to hypoxic stimuli were barely detectable at 17-20 degrees C, and were dramatically increased on warming to 36 degrees C. In contrast, responses to K(+)-induced depolarization were only slightly increased in rate of onset and recovery by warming. 4. The rise in [Ca2+]i originated largely from an intracellular store which was slowly depleted by exposure to nominally Ca2(+)-free solutions. Responses were unaffected by blockade of Ca2+ channels with organic (D600, verapamil) or inorganic (Co2+) blockers, by blockade of Na+ channels with tetrodotoxin (TTX), or by increasing action potential duration with tetraethylammonium (TEA). Responses to anoxia were increased by the increased [Ca2+]i loading that follows prior exposure to Ca2(+)-free solutions. 5. Responses to anoxia, to blockade of electron transport by CN-, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP), were equivalent in amplitude. The response to anoxia was occluded by concurrent application of FCCP, suggesting that the Ca2+ originates from the same pool in each case. 6. At 35-36 degrees C, responses to graded levels of PO2 were also graded. Thresholds varied between cells, but were typically 30-50 mmHg. Stimulus-responses curves were essentially hyperbolic, increasing dramatically as the PO2 approached 0 mmHg. 7. The sensitivity of cells to hypoxic solutions was increased by acidification of the superfusate over the pH range from 7.3 to 6.85. 8. Cell-attached patch clamp recordings showed depression of spontaneous action potentials associated with a rise in [Ca2+]i during exposure to anoxic solutions. Whole-cell recordings showed that anoxia increased a voltage-gated gK as described previously for CN-, while producing no change in resting conductance. 9. These data suggest that the rise in [Ca2+]i originates largely from Ca2+ efflux from a mitochondrial pool.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Responses of type I cells dissociated from the rabbit carotid body to hypoxia. 223 19

Optical fluorescence and reflectance measurements have been used to map the distribution of metabolic states in three dimensions in the gerbil brain with a spatial resolution of 200 microns an a time resolution of 4-6 s. In Mongolian gerbils anesthetized with pentobarbital, the redox states of the nicotinamide adenine dinucleotide (NADH) and flavoprotein components of the electron transport chain exhibit two distinct phases during the wave of spreading depression: (1) a transient period of oxidation and (2) a prolonged period of reduction, during which the cytochromes are reduced, and the hemoglobin is predominantly in the deoxy form. These data are interpreted as indicating that the energy demand placed on the gerbil brain during such spreading depression wave is sufficient to drive the brain temporarily hypoxic.
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PMID:Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain. 230 48

Initial Polytron treatment with subsequent exposure to the bacterial proteinase Nagarse has been shown to result in the isolation of two distinct populations of cardiac mitochondria, subsarcolemmal and interfibrillar mitochondria, respectively. Although these populations have been shown to possess distinct biochemical properties, few studies have been reported which document the potential differences in their response to pathological insult. We therefore examined the effect of acute hypoxia with or without reoxygenation as well as treatment with phosphate on oxidative phosphorylation on both groups of mitochondria. Freshly-isolated interfibrillar mitochondria (IFM) exhibited significantly higher respiratory values, with the exception of the ADP:O ratios, than subsarcolemmal mitochondria (SLM). With pyruvate-malate as respiratory substrate, 40 minutes hypoxia alone produced no effect on SLM whereas a stimulation in respiration was seen in IFM. A 40-minute reoxygenation period depressed the oxidative phosphorylation rate in SLM whereas it was stimulated in IFM. These treatments did not produce any effect in either population when succinate was the substrate of choice. Because of the latter observation, the possibility that increased lability of complex I of the electron transport chain accounted for the differences associated with NAD-linked substrates was studied by assessing NADH oxidation of sonicated mitochondria following the treatments. SLM exhibited enhanced permeability to exogenous NADH as well as increased sensitivity to sonication following either hypoxia or hypoxia/reoxygenation compared to IFM. Compared to hypoxia/reoxygenation, increasing concentrations of phosphate (5-15 mM) produced a marked depression in oxidative phosphorylation of SLM whereas IFM were relatively resistant. The toxic effects of phosphate were much more evident with pyruvate-malate as substrates; with succinate, oxidative phosphorylation of IFM was not depressed by phosphate whereas only a slight depression was observed with SLM. The latter population similarly exhibited reduced NADH oxidation following phosphate treatment whereas IFM were unaffected. Our studies show a differential sensitivity of two mitochondrial populations to hypoxia/reoxygenation, and, more markedly to phosphate. Since these effects were much less pronounced with succinate-linked respiration and since they were associated with defective NADH oxidation in SLM, it is suggested that the differences between the two populations may be accounted for by the increased lability of complex I of SLM due to hypoxia/reoxygenation or phosphate.
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PMID:Acute effects of hypoxia and phosphate on two populations of heart mitochondria. 260 32

The use of fluorescent calcium indicator, Indo-1, was evaluated for measuring changes in intracellular free calcium during electrical stimulation and anoxia in hippocampal slices. Fluorescence was measured from slices illuminated with brief (3 ns) light pulses (337 nm wavelength) from a nitrogen laser. This method of illumination produced more intense fluorescence than illumination with light from filtered xenon or mercury arc lamps, and prevented loss of electrical excitability encountered following continuous UV illumination. Background fluorescence in control slices (without Indo-1) was considerable, often approaching 50% of that obtainable after dye loading. A more serious concern, however, was that a large fraction (approximately 10%) of the background fluorescence was labile to both electrical stimulation and anoxia. This fluorescence results from changes in the reduction/oxidation (redox) state of nicotinamide adenine dinucleotide (NAD), which fluoresces in its reduced (NADH) but not oxidized (NAD+) form. Qualitative changes in free calcium could be measured by first determining the ratio of change in NADH fluorescence at 405 and 485 nm (the wavelengths of light used to measure calcium with Indo-1) prior to dye loading. Any arbitrary baseline could be selected as long as the ratio for the baseline at 405 and 485 nm was identical to that determined for labile NADH. By application of this compensation procedure, it was determined that intracellular calcium rose abruptly during the onset of anoxia and again during the spreading depression-like loss of ion homeostasis which inevitably occurred during anoxia in these slices.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indo-1 measurements of intracellular free calcium in the hippocampal slice: complications of labile NADH fluorescence. 272 10

The effect of the ganglioside GM1 was studied in a focal cerebral ischemia model in 30 cats consisting of 2 hours of middle cerebral artery occlusion followed by 4 hours of recirculation. The cerebrocortical electrical activity, extracellular potassium activity, and microcirculation indicated by NAD/NADH fluorescence were measured during occlusion as well as during recirculation in the core of the middle cerebral artery territory, while the cerebral metabolic rate for glucose (ICMRgl) was measured at the end of recirculation. The cats were classified into either mildly or moderately severe stroke groups based on the depression of the cerebrocortical electrical activity on the occluded side. Of 12 cats with only a mild stroke, six were administered GM1 intravenously 30 minutes after occlusion, while six cats were not treated. Of 12 cats with a moderate stroke, six were treated and six were left untreated. In six additional cats, only a sham insult was undertaken. In the cats with mild stroke, GM1 treatment significantly increased lCMRgl in the peripheral middle cerebral artery territory compared with the untreated cats; for the six treated cats, lCMRgl was normalized toward the control level, whereas it was depressed in the six untreated cats. There were no other significant effects of GM1 treatment on the other measured parameters. A potential protective effect of anesthesia is discussed.
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PMID:Effect of GM1 ganglioside after focal cerebral ischemia in halothane-anesthetized cats. 272 48

Cardiac depression in the isolated rat heart perfused with 4% ethanol was correlated with intracellular phosphate energetics and tissue water distributions. Energy metabolites were assessed using 31P magnetic resonance spectroscopy (MRS) and correlated to the mitochondrial redox state using epicardial surface fluorometry. Changes in myocardial water compartmentation were measured by using 1H NMR spectroscopy with an extracellular chemical-shift reagent (DyTTHA) and correlated to results of 2D echocardiography (2DE). During alcohol perfusion there was a significant decrease in developed pressure and in coronary flow. No change was seen in ATP, PCr, pHi, Pi, or NADH. After withdrawal of alcohol from the perfusate cardiac function reverted to control values without a depletion of energy levels. During alcohol perfusion 1H MRS showed a marked redistribution of water from the intra- to the extracellular space, corresponding to a 35% left ventricular wall thinning confirmed by 2DE. The results indicate that acute alcohol cardiac depression is related to a dehydration of myocardial cells, but is not associated with intracellular acidosis or energy depletion.
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PMID:31P and 1H magnetic resonance spectroscopy of acute alcohol cardiac depression in rats. 317 69

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/- 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.
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PMID:Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra. 333 7


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