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)

Energy metabolism of the heart in ischemia is mainly characterized by oxygen deficiency and lack of lactate removal. However, under certain circumstances substrate deficiency might contribute to disturbances of energy supply as well. Capillary permeability was determined from tracer washout kinetics of isolated hearts. Regulation of mitochondrial respiration was estimated from the relationship of phosphorylation potential vs. oxygen consumption. The results obtained suggest that at least under experimental conditions substrate supply at the level of capillary exchange can be a rate-limiting figure, as well as substrate supply at the mitochondrial level, i.e., NADH supply. The latter was inferred from the effects of cobalt and strontium ions on the regulation of respiration.
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PMID:States of myocardial metabolism related to ischemia. 740 68

In the present study, spontaneous and evoked release of selected amino acids in the rat spinal cord was studied using in vivo microdialysis. Perfusion of the microdialysis probe with 100 K+ evoked a 2-4-fold increase in release of the putative neurotransmitters aspartate, glutamate and taurine while glutamine was decreased. K(+)-evoked release of glutamate was almost completely Ca(2+)-dependent while that of aspartate was partially Ca(2+)-dependent. Taurine release was not affected by substituting Ca2+ with Co2+. Perfusion with 5 mM N-methyl-D-aspartate (NMDA) evoked 3-9-fold release of glutamate, glycine and taurine and a small increase in extracellular beta-alanine. No significant changes in glutamine and serine were found. 5 mM of the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced NMDA-evoked release of glutamate and taurine by approx. 50%. 5 mM 3-amino-1-hydroxypyrrolid-2-one (HA-966), an agonist at the glycine site of the NMDA receptor with very low efficacy, completely inhibited NMDA-evoked release of taurine and reduced the levels of released glutamate below baseline, similar to the effect of 1 mM CPP alone. The present results show that in situations of excessive release of excitatory amino acids such as spinal ischemia and trauma. NMDA receptor-evoked release of glutamate may amplify the deleterious process and spread the damage.
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PMID:In vivo studies on NMDA-evoked release of amino acids in the rat spinal cord. 758 Aug 74

Vessel growth is often associated with ischemia. VEGF, a potent angiogenic factor, has been shown to be induced by low oxygen concentrations. These studies were conducted to investigate the molecular basis of the hypoxia-induced increase in VEGF mRNA. Run-on analysis of VEGF revealed a minimal increase in the rate of gene transcription in a human retinal epithelial cell line grown under hypoxic conditions. Examination of VEGF mRNA stability revealed that the half-life of VEGF transcripts under normoxia was short, 30-45 min, but was dramatically increased to 6-8 h in cells grown under hypoxia. Cobalt chloride, which elevates VEGF and has been suggested to be similar to hypoxia in its mechanism of action, had only a slight effect on decay rate. We postulate that hypoxia-induced increases in mRNA stability provide the sustained increases in VEGF mRNA levels necessary to support a neovascular response.
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PMID:Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability. 765 77

A sustained high voltage-activated (HVA), nifedipine- and cadmium-sensitive calcium current and a sustained calcium action potential (AP) were recorded from horizontal cells isolated from catfish retina. pH indicator dyes showed that superfusion with NH4Cl alkalinized these cells and that washout of NH4Cl or superfusion with Na-acetate acidified them. HVA current was slightly enhanced during superfusion of NH4Cl but was suppressed upon NH4Cl washout or application of Na-acetate. When 25 mM HEPES was added to the patch pipette to increase intracellular pH buffering, the effects of NH4Cl and Na-acetate on HVA current were reduced. These results indicated that intracellular acidification reduces HVA calcium current and alkalinization increases it. Sustained APs, recorded with high resistance, small diameter microelectrodes, were blocked by cobalt and cadmium and their magnitude varied with extracellular calcium concentration. These results provide confirmatory evidence that the HVA current is a major component of the AP and indicate that the AP can be used as a measure of how the HVA current can be modified in intact, undialyzed cells. The duration of APs was increased by superfusion with NH4Cl and reduced by washout of NH4Cl or superfusion with Na-acetate. The Na-acetate and NH4Cl washout-dependent shortening of the APs was observed in the presence of intracellular BAPTA, a calcium chelator, IBMX, a phosphodiesterase inhibitor, and in Na-free or TEA-enriched saline. These findings provide supportive evidence that intracellular acidification may directly suppress the HVA calcium current in intact cells. Intracellular pH changes would thereby be expected to modulate not only the resting membrane potential of these cells in darkness, but calcium-dependent release of neurotransmitter from these cells as well. Furthermore, this acidification-dependent suppression of calcium current could serve a protective role by reducing calcium entry during retinal ischemia, which is usually thought to be accompanied by intracellular acidosis.
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PMID:Modulation of a sustained calcium current by intracellular pH in horizontal cells of fish retina. 768 44

Effects of 60 and 120 minutes of in-vitro ischaemia on the localization of xanthine oxidase activity were studied in rat intestine and liver. A histochemical method was applied on unfixed cryostat sections using a semipermeable membrane. The incubation medium contained hypoxanthine as substrate, cerium ions which capture the enzyme product, hydrogen peroxide, and sodium azide to inhibit catalase and peroxidase activities. In a second step reaction diaminobenzidine was polymerized in the presence of cobalt ions and hydrogen peroxide by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in the cytoplasm of enterocytes and goblet cells of control small intestine. When the incubation was performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase activity, no reaction product was found. After 60 and 120 minutes of storage of tissue blocks at 37 degrees C enzyme activity was significantly reduced in the apical region of epithelial cells, whereas a high activity was present in the basal region of these cells. A very low xanthine oxidase activity was found in rat liver. Highest activity was present in endothelial cells, whereas in liver parenchymal cells, a more pronounced activity was found in pericentral than in periportal hepatocytes. Ischaemia up to 120 minutes did not affect the enzyme activity in livers. It was concluded that increased xanthine oxidase activity during ischaemia may not be responsible for cell damage during reperfusion in contrast with assumptions in the literature.
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PMID:The effect of ischaemia on xanthine oxidase activity in rat intestine and liver. 847 32

Between May 1, 1986 and May 31, 1992 at the University of Minnesota, we interpreted 129 renal allograft biopsy specimens (done in 48 grafts during the first 6 months posttransplant) as showing changes consistent with chronic rejection. For this retrospective analysis, we reexamined these biopsies together with clinical information to determine: (a) whether a diagnosis other than chronic rejection would have been more appropriate, (b) how early posttransplant any chronic rejection changes occurred, and (c) if the diagnosis correlated with outcome. We found that (1) chronic rejection is uncommon in the first 6 months posttransplant; it was documented in only 27 (2.4%) of 1117 renal allografts and was preceded by acute rejection in all but 3 recipients (for these 3, the first biopsy specimen showed both acute and chronic rejection). (2) Chronic vascular rejection was seen in 1 recipient as early as 1 month posttransplant; the incidence increased over time and was associated with an actual graft survival rate of only 35%. (3) The most frequent cause of arterial intimal fibrosis in the first 6 months posttransplant was arteriosclerotic nephrosclerosis (ASNS) of donor origin. Long-term graft function for recipients with ASNS was 67%. (4) Early-onset ischemia or thrombosis was seen in 14 recipients and predicted poor outcome: only 35.7% of these recipients had long-term graft function. (5) Cyclosporine (CsA) toxicity was implicated in only 3 recipients, who had mild diffuse interstitial fibrosis in association with elevated CsA levels. Other variables (including systemic hypertension, urinary tract infection, obstructive uropathy, neurogenic bladder, cobalt therapy, and recurrent disease) were not significantly associated with chronic renal lesions in the first 6 months posttransplant. A significant number of biopsies were originally interpreted as showing chronic rejection, but the diagnosis was changed upon reevaluation in conjunction with clinical data. We conclude that many factors coexist to produce chronic lesions in biopsies during the first 6 months posttransplant, so clinical correlation is needed before establishing a diagnosis of chronic rejection.
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PMID:Chronic renal allograft rejection in the first 6 months posttransplant. 854 66

Activity of xanthine oxidoreductase (total xanthine dehydrogenase plus xanthine oxidase) and xanthine oxidase was determined cytophotometrically in periportal and pericentral areas of livers of rats under various (patho)physiological conditions that are known to affect the content of reduced glutathione. For this purpose, rats were either normally fed or fasted for 24 hours, fasted for 24 hours, and treated with diethylmaleate that depleted glutathione or treated by in vivo ischemia for 2 hours in the livers. Xanthine oxidoreductase activity was shown histochemically with the use of a tetrazolium salt procedure, and xanthine oxidase activity was localized with a cerium-diaminobenzidine-cobalt-hydrogen peroxide technique in unfixed cryostat sections of the livers. Cytophotometric measurements showed that total xanthine oxidoreductase activity was decreased after fasting and ischemia, whereas only ischemia caused reduced xanthine oxidase activity. Moreover, the percentage of xanthine oxidase of total xanthine oxidoreductase activity was constant in both periportal and pericentral areas at the level of approximately 4% in normally fed and 24-hour fasted and diethylmaleate-treated rats. Ischemia reduced this percentage in both areas of the liver to 2%. It was concluded that the amount of endogenous reduced glutathione did not affect the percentage of xanthine oxidase. The low percentage of xanthine oxidase as determined in the present in situ histochemical study indicates that in vivo the percentage oxidase in rat liver is lower than is assumed on the basis of biochemical assays in liver homogenates even after strictly controlled homogenization procedures. Apparently, conversion of xanthine dehydrogenase into xanthine oxidase may occur in vitro to yield percentages of xanthine oxidase of 10%-20% as are reported in the literature. The latter increase in the percentage of xanthine oxidase may be caused by changes in the local environment of the enzymes, which is left completely intact in histochemical assays. The finding of this low percentage of xanthine oxidase further stresses that the main function of xanthine oxidoreductase in the liver is not the production of superoxide anion radicals and/or hydrogen peroxide but rather the metabolism of xanthine to uric acid, which can act as a potent antioxidant.
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PMID:The proportion of xanthine oxidase activity of total xanthine oxidoreductase activity in situ remains constant in rat liver under various (patho)physiological conditions. 890 95

This study investigated the vascular effect of ferromagnetic obstruction of cochlear blood vessels in the guinea pig using dual-channel laser Doppler flowmetry. To improve this technique, we tested new types of magnets and iron spheres. In so doing, the cochlear temperature was lowered selectively and general hypothermia was avoided. The success of vascular impairment in the inner ear was found to depend on the experimental conditions used. Given normothermic conditions (38 degrees C body temperature), a clear reduction in cochlear blood flow (CBF) was found in only about 30% of the animals tested when an aluminium-nickel-cobalt alloy magnet and carbonyl iron spheres were used, while this ratio increased to about 80% under general hypothermia (33 degrees C). Using a stronger neodymium-iron-boron magnet and smaller-sized iron spheres, we found the success of vascular obstruction to be approximately 70% under normothermia and 100% with local hypothermia (to 33 degrees C) of the cochlea. Although the extent of vascular impairment revealed a considerable interindividual variation, the present findings demonstrate that ferromagnetic intervention in CBF with dual-channel laser Doppler flowmetry can be used to investigate the effect of quantified cochlear ischemia on inner ear physiology in the guinea pig model and test various therapeutic strategies.
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PMID:Laser Doppler measurements of inner ear blood flow during experimental thrombosis of cochlear blood vessels in the guinea pig. 906 62

It has been hypothesized that inadequate placentation in the hypertensive disorder of pregnancy known as preeclampsia creates foci of placental ischemia/hypoxia leading to the elaboration of factors that compromise systemic endothelial function to produce disease sequelae. As tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1) are inflammatory cytokines capable of eliciting endothelial cell dysfunction, we investigated whether the production of these inflammatory cytokines by cultured villous explants from the human placenta was affected by incubation in reduced oxygen (2% O2). The term placenta produced TNF alpha, IL-6, and low levels of IL-1alpha and IL-1beta under standard tissue culture conditions. Hypoxia significantly increased TNF alpha, IL-1alpha, and IL-1beta production by 2-, 6-, and 23-fold, respectively, but did not affect IL-6 production. Further, cytokines were immunolocalized to the syncytiotrophoblast layer as well as to some villous core cells. Hypoxic regulation of placental TNF alpha and IL-1beta production also appeared to differ based on gestational age. Finally, treatment with either cobalt chloride or an iron chelator mimicked the hypoxic response, suggesting that stimulation of placental cytokine production may involve a heme-containing, O2-sensing protein. These results suggest that placental hypoxia can lead to the elaboration of inflammatory cytokines, which may contribute to the pathophysiology of preeclampsia.
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PMID:Hypoxia stimulates cytokine production by villous explants from the human placenta. 914 53

In CA1 pyramidal neurons in rat hippocampal tissue slices, superfusion with ischemia-simulating medium produced a rapid depolarization after 6 min of exposure. The membrane potential eventually reached 0 after 5 min (a persistent depolarization), even when oxygen and glucose were reintroduced. The role of various ions in the reversal of this persistent depolarization after reintroduction of oxygen and glucose was investigated. The peak of the persistent depolarization was decreased in solutions containing reduced Na+ or Ca2+ and in solutions containing Co2+ or Ni2+. In contrast, the depolarization was not affected by reduction of external K+ or Cl- or by addition of tetrodotoxin (TTX), flunarizine, or nifedipine. These results suggest that sustained Na+ and Ca2+ influxes produce the persistent depolarization. The membrane potential recovered after reintroduction of oxygen and glucose in low Ca2+, low Cl-, or K+-rich medium and in TTX- or tetraethylammonium-containing medium, but not in low Na+ or low K+ medium and in flunarizine- or nifedipine-containing medium. Either reduction in extracellular Ca2+ or addition of Co2+ was the most effective in promoting recovery from the persistent depolarization, suggesting that Ca2+ influx has a key role in causing the membrane dysfunction. The peak of the persistent depolarization was reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonopentanoic acid (AP5), DL-amino-3-phosphonopropionic acid (AP3), or DL-amino-4-phosphonobutyric acid, suggesting that activation of non-N-methyl-D-aspartate (non-NMDA), NMDA, and metabotropic glutamate (Glu) receptors is involved in the generation and maintenance of the persistent depolarization. Among these Glu receptor antagonists, only CNQX or AP5 was able to reduce dose dependently the level of depolarization, suggesting that Ca2+ influx via both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate type II receptors and NMDA receptors contributes to the membrane dysfunction. trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) did not affect the peak potential of the persistent depolarization, but it dose-dependently restored the membrane potential. AP3 antagonized the protective action of t-ACPD. The membrane potential also recovered after reintroduction when the slice was pretreated by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, ryanodol 3-(1H-pyrrole-2-carboxylate), 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, and procaine, suggesting that raised [Ca2+]i from Ca2+-induced Ca2+ release pool contributes to the membrane dysfunction. It, therefore, is concluded that raised [Ca2+]i has a dominant role in causing irreversible changes. The increase in [Ca2+]i during the persistent depolarization may be the result of Ca2+ entry via both a leaky membrane and Glu-activated receptor channels as well as Ca2+ released from internal stores.
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PMID:Factors that reverse the persistent depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro. 930 23


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