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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the relationship of increased capillary network resistance due to leukocyte-capillary plugging and tissue edema through macromolecular leakage to tissue injury after ischemia-reperfusion (I/R). After a 3-h complete ischemia in the dorsal skinfold chamber of the awake Syrian hamster, the following parameters were measured: vessel diameter, macromolecular leakage, erythrocyte velocity, adherent leukocytes, rolling leukocytes, freely flowing leukocytes, functional capillary density (FCD), propidium iodide (PI)-positive cell nuclei, and increase in network flow resistance due to leukocyte-capillary plugging. These measurements were made under baseline conditions and after 0.5 and 2 h of reperfusion for I/R alone, I/R with phalloidin (PL) treatment (to block leakage), and I/R with both PL and cytochalasin D (CD) (to block both leakage and plugging). Neither treatment had an effect on the leukocyte adherence or rolling. PL treatment preserved the endothelial barrier, improved FCD, and reduced the amount of PI measured tissue damage. CD treatment eliminated the increase in network resistance due to leukocyte plugging but did not improve FCD or tissue damage. Thus, in this I/R model, macromolecular leakage plays a role in tissue injury, whereas leukocyte plugging does not appear to be an important mechanism.
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PMID:Role of leukocyte plugging and edema in skeletal muscle ischemia-reperfusion injury. 927 19

We describe two Caucasian women with the concurrence of Graves' disease and the moyamoya phenomenon (radiological evidence of collateral cerebral blood vessels like "puffs of smoke" due to cerebrovascular occlusive disease). One patient presented with acute cerebrovascular ischemia due to Moyamoya disease shortly after radioactive iodine therapy for Graves' disease and the second presented with Graves' disease 10 years after being diagnosed with moyamoya dysplastic cerebral vessels. The optimal treatment of hyperthyroidism in these patients is unknown; however, careful control of the hyperthyroidism by any modality seems reasonable. Our limited experience suggests that antithyroid drugs and radioactive iodine therapy are rational options. Thyroidectomy appears to be a safe therapeutic alternative, although long-term efficacy may be difficult to assure. Both of our patients had to be treated twice for hyperthyroidism. Whether Graves' disease and Moyamoya coexist because of an aggressive autoimmune mechanism is a concept that remains to be settled.
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PMID:Concurrence of Graves' disease and dysplastic cerebral blood vessels of the moyamoya variety. 929 53

Recent and future evolutions in neuroSPECT apply to radiopharmaceuticals techniques and the synergistic use of different imaging modalities in the work-up of neurological disorders. The introduction of Technetium labelled perfusion tracers, which could pass the intact blood-brain barrier, together with the implementation of the tomographic principle, by making the conventional gamma camera rotating, enabled estimation of regional cerebral blood flow and indirectly of local brain metabolism. In addition at present Thallium-201 and Tc-99m sestaMIBI allow functional detection of viable tumor tissue, without interference from previous surgery or radiotherapy as seen using CT-scan or MRI. In neurology this has led to the recognition of SPECT by the American Academy of Neurology (Therapeutics and technology subcommittee) as an established or promising tool in major neurological disorders such as dementia, stroke and epilepsy, while other domains such as brain oncology are considered investigational. With regard to radiopharmaceuticals, recent evolutions mainly include the development of mostly Iodine-123 labelled receptor ligands, some of which are already commercially available. For instrumentation advances consist e.g. of multidetector systems equipped with fanbeam collimators, attenuation and scatter correction or coincidence detection. Given the present role for nuclear neurology it may be expected that these additional radiopharmaceutical and technical innovations will continue to stimulate the development of SPECT of the brain. The synergistic use of several imaging techniques such as CT, (functional) MRI, source imaging, SPECT and PET represents a multimodal holistic approach to probe cerebral functions for research and clinical purposes. Clinical indications, in which this synergistic use is illustrated include e.g. support of the clinical diagnosis of dementia of the Alzheimer type, presurgical ictal detection of seizure focus, detection of acute ischemia and differential diagnosis between radiation necrosis and brain tumor recurrence. The synergistic use of imaging modalities, optimally applied using image fusion, allows to overcome the intrinsic limitations and to enhance the specific advantages of the different approaches as it leads to increased precision and accuracy, as well for spatial anatomofunctional correlation as for quantification.
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PMID:Recent and future evolutions in NeuroSPECT with particular emphasis on the synergistic use and fusion of imaging modalities. 934 86

Myocardial protection is usually studied in vitro on perfused heart preparations, but never directly on cultured cardiomyocytes. We evaluated a model of cultured newborn rat cardiomyocytes to study both the cytotoxicity and the protective effect against chemical hypoxia of three cardioplegic solutions (St Thomas' I, Bretschneider, St Thomas' II) under normothermic (37 degrees C) and hypothermic (4 degrees C) conditions. Cytotoxicity was evaluated in 50% and 100% concentrations of the cardioplegic solutions with incubation times from 90 to 360 min. Myocardial protection was studied in 50% cardioplegic solution with metabolic inhibitors. Immediate and late viabilities, after 24 h of recovery in the medium, were evaluated by simultaneous staining with fluorescein diacetate and propidium iodide. At 37 degrees C, the 50% concentration of the three cardioplegic solutions did not modify cell viability. At 37 degrees C, with 360 min of incubation, the 100% concentration of the St Thomas' I and Bretschneider solutions diminished immediate viability (mean +/- SD; medium 87% +/- 2%; St Thomas' I 58% +/- 5%; Bretschneider 37% +/- 8%; St Thomas' II 89% +/- 3%) as well as late viability (medium 69% +/- 2%; St Thomas' I 32% +/- 3%; Bretschneider 24% +/- 7%; St Thomas' II 65% +/- 4%). At 4 degrees C, immediate and late viabilities were unaffected by cardioplegic solutions. At 37 degrees C, after 360 min incubation time, metabolic inhibitors diminished immediate viability to 29% +/- 1% and late viability to zero. None of the three cardioplegic solutions used at 50% concentration prevented this effect. At 4 degrees C, immediate viability was not significantly affected by metabolic inhibitors (73% +/- 10%), but the use of Bretschneider cardioplegic solution seemed to be detrimental (53% +/- 9%). On the other hand, recovery phase after pretreatment with metabolic inhibitors with or without cardioplegic solutions for 360 min significantly diminished late viability (medium 63% +/- 7%; metabolic inhibitors 17% +/- 8%; St Thomas' I 17% +/- 6%; Bretschneider 8% +/- 6%; St Thomas' II 15% +/- 3%) and again cardioplegia was inefficient. In conclusion, in this in vitro model for the study of cardioplegic solutions, only pure concentrations of the St Thomas' I and Bretschneider solutions under normothermic conditions were cytotoxic. The well-known protective effects of hypothermia against ischemia and reperfusion injury were both reproduced. Therefore, and even though cardioplegia failed to have any protective effect, probably owing to a severe metabolic inhibition, this model may be useful for studying myocardial protection.
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PMID:Validity of a model of cultured myocardial cells for assessment of cardioplegia. 935 21

Organotypic cultures of the brain provide a unique opportunity to directly examine the regional vulnerability of specific brain regions like the hippocampus. Two well-characterized models of oxidative stress were used to examine the regional vulnerability of the hippocampus. Endogenous oxidative stress was induced by blocking synthesis of the endogenous antioxidant, glutathione with buthionine sulfoximine (BSO). Exogenous oxidative stress was induced with paraquat, an intracellular generator of superoxide. Injury was measured by quantitative fluorescence microscopy using the vital dye propidium iodide. BSO caused dose- and time-dependent injury that took at more than 24 h to develop. Injury began in discrete patches in the culture. In any given culture, each patch increased in size and intensity as incubation continued. The pattern was not clearly correlated with neuronal anatomy and may demonstrate glial vulnerability. Injury caused by BSO could be prevented with the antioxidants trolox or the 21-aminosteroid U-83836E, both of which are vitamin E derivatives. Paraquat also caused dose- and time-dependent injury, but the CA1 region of the hippocampus was most vulnerable. The same pattern of selective CA1 injury was caused by brief exposures to high concentrations and by prolonged exposures to much lower concentrations. Under some conditions, paraquat injury was prevented by iron chelation with deferoxamine or by blockade of either NMDA or AMPA/ kainate glutamate receptors. During paraquat exposure, glutathione concentration in the cultures was reduced prior to onset of propidium staining. The observation that the hippocampus has a similar selective regional pattern of vulnerability to paraquat and ischemia suggests that their mechanisms of injury may be related.
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PMID:Regional vulnerability to endogenous and exogenous oxidative stress in organotypic hippocampal culture. 945 20

We determined the functional role of nitric oxide (NO) and endothelins (ET), two potent vasoactive mediator systems in the liver, for the pathogenesis of sinusoidal perfusion failure and lethal hepatocyte injury after low-flow ischemia/reperfusion in the isolated perfused rat liver. NO synthase blockade with Nomega-nitro-L-arginine methyl ester (L-NAME) (10[-3] mol/L) before reperfusion prevented increased N02-/NO3- the final products of NO oxidation, which could be observed in the vehicle group. Epifluorescence microscopy revealed that the decrease in functional sinusoid density during reperfusion was much more profound compared with vehicle. This was associated with a lower surface PO2, a substantially higher number of nonviable hepatocytes, as assessed by in situ propidium iodide staining, and enhanced enzyme release into the perfusate compared with vehicle. In contrast, reperfusion in the presence of the endothelinA+B receptor antagonist bosentan (2 x 10(-4) mol/L) restored functional sinusoid density and surface PO2 to baseline values, resulted in a small reduction in the number of propidium iodide-positive hepatocytes, and caused similar increases in enzyme release as compared with vehicle. This indicates that hepatic generation of NO attenuates sinusoidal perfusion failure and improves liver tissue oxygenation, thus limiting hepatocyte injury during early reperfusion after hepatic low-flow ischemia. In contrast, endothelins counteract the microcirculatory effects of NO, i.e., mediate the no-reflow in hepatic sinusoids; however, the restoration of functional sinusoid density with bosentan resulted only in a small reduction in tissue damage, suggesting that additional components, which are independent of microcirculatory failure, contribute to hepatic reperfusion injury under these conditions.
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PMID:Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat. 950 Jul 4

Recently we developed a model of cyclosporine nephropathy in rats characterized by tubulointerstitial (TI) injury, macrophage infiltration, and progressive interstitial fibrosis [1, 2]. To determine if the TI injury accompanying cyclosporine A (CsA) nephropathy was associated with accelerated apoptosis and ischemia, we treated rats for five weeks with CsA with or without losartan (to block angiotensin II type 1 receptor), or hydralazine/furosemide (H/F) (protocol #1). In protocol #2, rats received CsA with or without L-NAME (to block nitric oxide) or L-arginine (to provide a precursor to nitric oxide formation). Cyclosporine A treated rats had increased apoptosis of tubular and interstitial cells documented by PAS, propidium iodide staining, TUNEL assay, and electron microscopy compared to vehicle treated controls. Macrophages containing apoptotic cells could be confirmed by TUNEL/ED-1 doublestaining and colocalized in areas of TI injury. Animals treated with CsA + losartan had a statistically significant decrease in apoptosis (TUNEL + cells/mm2) when compared to CsA treated animals (6.0 vs. 19.9, P < or = 0.0001). The decrease in apoptosis in the CsA + H/F group was not statistically significant. Animals treated with CsA + L-NAME had a statistically significant increase in apoptosis compared to the CsA treated animals (12.3 vs. 6.4, P = 0.001). L-arginine administration with CsA resulted in a decrease in tubulointerstitial apoptosis versus CsA treated animals, however, this did not reach statistical significance. The addition of L-arginine did result in a significant reduction in interstitial fibrosis (P < 0.0001). Regression analysis revealed a significant correlation between apoptosis and interstitial fibrosis in both protocols. (CsA vs. CsA + losartan r = 0.63, P < 0.0001; CsA vs. CsA + L-NAME r = 0.83, P < 0.0001). We conclude that CsA nephropathy is associated with a marked increase in apoptosis of tubular and interstitial cells. Cyclosporine A induced apoptosis is partially mediated by angiotensin II and nitric oxide inhibition, suggesting a role for renal ischemia in this process, and CsA induced apoptosis correlates with interstitial fibrosis.
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PMID:Accelerated apoptosis characterizes cyclosporine-associated interstitial fibrosis. 955 96

We hypothesize that lung ischemic injury is related to cessation of flow leading to endothelial cell membrane depolarization and activation of oxidant-generating systems. Cell membrane potential was assessed in isolated, oxygen ventilated, Krebs-Ringer bicarbonate buffer-dextran-perfused rat lungs by lung surface fluorescence after infusion of bis-oxonol or 5,5',6,6'-tetrachloro-1, 1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1), voltage-sensitive dyes. Surface fluorometry showed increased bis-oxonol fluorescence (34.7 +/- 3.3% above baseline) and decreased JC-1 fluorescence (24.5 +/- 4.5% below baseline) with ischemia, compatible with membrane depolarization. Fluorescence change was initiated within 1-2 min of the onset of ischemia and was rapidly reversible with reperfusion. Fluorescence changes varied with perfusion flow rate; maximal increase occurred with the transition from 1.8 ml/min to zero flow. Elevation of static intravascular pressure resulted in only a minor increase of bis-oxonol fluorescence. In situ subpleural fluorescence microscopy showed that endothelial cells are the major site of the increased bis-oxonol fluorescence signal with ischemia. These results indicate that endothelial cell membrane depolarization represents an early event with lung ischemia. Since the adenosine triphosphate content of lung was unchanged with ischemia in the O2-ventilated lungs, we postulate that membrane depolarization results from elimination of shear stress, possibly via inactivation of flow-sensitive K+-channels.
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PMID:ATP-independent membrane depolarization with ischemia in the oxygen-ventilated isolated rat lung. 956 35

Since the sphingomylein-ceramide-sphingosine pathway, especially ceramide, has been shown to induce programmed cell death (apoptosis), and since apoptosis may be involved with ischemic/reperfused injury in the heart, it became desirable to quantitate the three components in ischemic/reperfused rat heart. One group of rat hearts (n = 6) was isolated and perfused with Krebs-Henseleit buffer using the Langendorff non-recirculating mode. The hearts were perfused for 10 min, made ischemic for 30 min and reperfused for 120 min. Hearts were collected and stored at - 70 degrees C before ischemia, after ischemia and after 30, 60 and 120 min of reperfusion. The hearts were homogenized, and lipids were extracted using the Folch method. The lipids were then chromatographed on Whatman silica gel 60 A high-performance thin-layered chromatography (HPTLC) plates. The plates were developed with iodine, photographed using Photoshop software and quantitated using NIH Imaging software. The results show a 50% decrease of sphingomylein during reperfusion with a corresponding increase in ceramide with sphingosine showing a smaller decrease as compared with the ceramide increase.
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PMID:HPTLC analysis of sphingomylein, ceramide and sphingosine in ischemic/reperfused rat heart. 957 36

We determined if changes in intraneuronal Cl- occur early after ischemia in the hippocampal slice. Slices from juvenile rats (14-19 days old) were loaded with the cell-permeant form of 6-methoxy-N-ethylquinolinium chloride (MEQ), a Cl(-)-sensitive fluorescent dye. Real-time changes in intracellular chloride concentration ([Cl-]i) were measured with UV laser scanning confocal microscopy in multiple neurons within each slice. In vitro ischemia (26-28 degrees C, 10 min) was confirmed by the loss of synaptic transmission (evoked field excitatory postsynaptic potentials) from pyramidal cells in area CA1. After ischemia and reoxygenation (10 min), MEQ fluorescence decreased significantly in CA1 pyramidal cells and interneurons. The decreased fluorescence corresponded to an ischemia-induced increase in [Cl-]i of approximately 10 mM. Pretreatment with the GABA(A)-gated Cl- channel antagonist picrotoxin (100 microM) blocked the ischemia-induced change in [Cl-]i. Analysis of the superfusates indicated that ischemia also caused a transient amino acid (GABA, glutamate, and aspartate) release that was maximal at approximately 10 min, returning to baseline shortly thereafter. Recovery from ischemia was confirmed by the return of synaptic transmission in area CA1, the return toward baseline of the ischemia-induced decrease in MEQ fluorescence, and exclusion of propidium iodide from MEQ fluorescent cells. Furthermore, pyramidal cells did not undergo cell swelling during this early phase of reoxygenation, as indicated by the volume-sensitive dye calcein. Thus, mild ischemia induces the accumulation of [Cl-]i secondary to GABA(A) receptor activation, in the absence of cellular swelling or death. In contrast, depolarization of the slice with K+ (50 mM) decreased MEQ fluorescence significantly but caused cell swelling. Picrotoxin did not prevent the K+-induced increase in [Cl-]i. It is possible that an increased [Cl-]i, following either an ischemic event or an episode of depolarization, would reduce the Cl- driving force and thereby limit synaptic transmission by GABA. To support this hypothesis, ischemia caused a reduction in the ability of the GABA agonist muscimol to increase [Cl-]i after 20-min reoxygenation.
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PMID:Optical imaging of hippocampal neurons with a chloride-sensitive dye: early effects of in vitro ischemia. 960 15


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