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

The effects of intestinal ischemia and reperfusion (I/R) on small intestinal mucosal endothelial and epithelial barrier integrity and phagocytic function were assessed in rats subjected to 20- or 40-min mesenteric ischemia and a 3-h reperfusion. The results showed that human serum albumin (125I-HSA) flux through the endothelial layer to the interstitial space increased as did 125I-HSA clearance from blood to the gut lumen and 131I-HSA flux from the gut lumen to the interstitial space in rats with I/R. E. coli adhering to microvilli, invading and passing into the microvessels, were noted on the small intestinal mucosa in animals subjected to 40-min ischemia and a 3-h reperfusion. Phagocytic function increased, especially in the small intestinal wall, lungs, liver, and spleen in the groups with I/R, correlating with the length of ischemia. The results imply that both endothelial and epithelial barrier integrity is impaired in the early phase after I/R and that the epithelial barrier more effectively restricts macromolecular leakage compared with the endothelial barrier. I/R impairs the intestinal barrier not only by causing tissue hypoxia but also by activating the phagocytic system and aggravating barrier damage, which finally may result in bacterial translocation and remote organ dysfunction.
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PMID:Phagocytic and intestinal endothelial and epithelial barrier function during the early stage of small intestinal ischemia and reperfusion injury. 1071 78

Changes in brain temperature are known to modulate the marked neuronal damage caused by an approximately 10-min intra-ischemic period. Numerous studies have suggested that the extracellular glutamate concentration ([Glu](e)) in the intra-ischemic period and the initial postischemia period is strongly implicated in such damage. In this study, the effects of intra-ischemic brain temperature (32, 37, 39 degrees C) on [Glu](e) were investigated utilizing a dialysis electrode combined with ferrocene bovine serum albumin (BSA), which allows oxygen-independent real-time measurement of [Glu](e). This system allowed separate quantitative evaluation of intra-ischemic biphasic glutamate release from the neurotransmitter and metabolic pools, and of postischemic glutamate re-uptake in ischemia-reperfusion models. The biphasic [Glu](e) elevation in the intra-ischemic period did not differ markedly among intra-ischemic brain temperatures ranging from 32 to 39 degrees C. Intra-ischemic normothermia (37 degrees C) and mild hyperthermia (39 degrees C) markedly inhibited [Glu](e) re-uptake during the postischemic period, although the intra-ischemic [Glu](e) elevation did not differ from that during intra-ischemic hypothermia (32 degrees C). It was assumed that normothermia or mild hyperthermia in the intra-ischemic period influences intracellular functional abnormalities other than the intra-ischemic [Glu](e) elevation, thereby inhibiting glutamate re-uptake after reperfusion rather than directly modulating intra-ischemic [Glu](e) dynamics.
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PMID:Quantitative evaluation of extracellular glutamate concentration in postischemic glutamate re-uptake, dependent on brain temperature, in the rat following severe global brain ischemia. 1079 87

Various kinds of acute pathological events in the central nervous system, such as ischemia, hemorrhage, and trauma, often cause brain edema. The edema may advance for days or weeks while inducing extensive damage in neural function, regardless of the extent of the original damage, and often results in death. Delayed edema is thought to be vasogenic; however, the mechanism underlying edema induction remains unknown. We found delayed vascular cell proliferation with a blood-brain barrier breakdown in and around the gerbil CA1 hippocampus, a region known to be involved in delayed apoptotic neuronal death 2-6 days after transient ischemia. Vascular cell proliferation, assessed by (3)H-thymidine incorporation, was most prominent 4-6 days after ischemia, and extravasation of exogenously applied dye or endogenous serum albumin from blood vessels was observed concomitantly. We propose neovascularization in delayed neuronal death as a cause of brain edema advancing days after neurological events.
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PMID:Neovascularization with blood-brain barrier breakdown in delayed neuronal death. 1087 57

Nitric oxide-releasing drugs have been shown to reduce ischemia/reperfusion (I/R) injury by acting as radical scavengers. However, their therapeutic application is hampered by specific side effects and rapid bioreduction in vivo. The half-life and antioxidant activity of nitroxides may be enhanced by their covalent binding to human serum albumin, resulting in polynitroxyl albumin (PNA). Thus, PNA may represent a novel antioxidative drug. The objectives of this study were to elucidate 1) whether PNA is able to diminish I/R injury; 2) the most effective dose of PNA in vivo; and 3) whether the addition of the nitroxide tempol enhances and/or prolongs the effect of PNA. Experiments were performed using a 4-h tourniquet-induced ischemia model in the hamster dorsal skinfold chamber. In the first part, five groups (n = 6) of animals received an infusion of 1) 1% body weight (b.w.) saline (0.9%); 2) 0.5% b.w. albumin (20%); 3) 0.5% b.w. PNA (20%); 4) 1% b.w. albumin (20%); and 5) 1% b.w. PNA (20%) 15 min prior to reperfusion. In the second part of the study, tempol (17 mg/mL) was added either to albumin or PNA (1:9), and 0.5% b.w. of this solution was infused (Group 6: tempol + albumin 0.5% b.w.; Group 7: tempol + PNA 0.5% b.w.). Intravital fluorescence microscopy allowed for quantification of functional capillary density (FCD), leukocyte adherence, extravasation of fluorescein isothiocyanate-labeled Dextran and non-viable (Propidium-positive) cell count prior to ischemia and 0.5 h, 2 h, and 24 h after reperfusion. PNA and--to a lesser extent albumin--effectively reduced postischemic microvascular perfusion failure, leukocyte adhesion, and tissue injury. PNA was most effective in the dose 1% b.w. Although free oxygen radical scavenging seems to be an underlying mechanism leading to the beneficial effects of PNA on I/R injury, hemodilution and known radical scavenging properties of pure albumin contribute in part to the observed effects. Although the combination of tempol and PNA revealed further short-term effects on microvascular perfusion and leukocyte adhesion, it did not result in a long-term improvement of tissue injury.
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PMID:Impact of polynitroxylated albumin (PNA) and tempol on ischemia/reperfusion injury: intravital microscopic study in the dorsal skinfold chamber of the Syrian golden hamster. 1094 61

Stable nitroxyl radicals (nitroxides) are potential antioxidant drugs, and we have previously reported that linking nitroxide to biological macromolecules can improve therapeutic activity in at least two ways. First, polynitroxylated compounds such as polynitroxyl human serum albumin (PNA) are a novel class of high molecular weight, extracellular antioxidants. Second, compounds such as PNA can prolong the half-life of free (unbound, low molecular weight) nitroxides such as 4-hydroxy-2,2,6, 6-tetramethylpiperidine-N-oxyl (Tempol) in vivo. Unlike PNA, Tempol can readily access the intracellular compartment. Thus PNA can act alone in the extracellular compartment, or in concert with Tempol, to provide additional antioxidant protection within cells. In this study, we compared the abilities of PNA, Tempol, and the combination of PNA + Tempol to prevent lung microvascular injury secondary to prolonged gut ischemia (I, 120 min) and reperfusion (R, 20 min) in the rat. Pulmonary capillary filtration coefficient (K(f,c)) and lung neutrophil retention (tissue myeloperoxidase activity, MPO) were measured in normal, isolated rat lungs perfused with blood harvested from I/R rats. Blood donor rats were treated with drug during ischemia. Gut I/R resulted in a marked increase in pulmonary capillary coefficient and lung MPO. PNA + Tempol, but not PNA alone or Tempol alone, at the doses used, prevented the development of lung leak. None of the treatments had an effect on lung neutrophil retention. Anti-inflammatory therapeutic activity appeared to correlate with blood Tempol level: in the presence of PNA, blood Tempol levels were maintained in the 50-100 microM range vs. essentially undetectable levels shortly after Tempol was administered alone. In this model of lung injury secondary to prolonged gut I/R, lung capillary leak was prevented when the membrane-permeable compound Tempol was maintained in its active, free radical state by PNA.
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PMID:Polynitroxyl-albumin (PNA) plus tempol attenuate lung capillary leak elicited by prolonged intestinal ischemia and reperfusion(1). 1096 4

We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU </= 0.400). Further studies are warranted to determine if an assay measuring altered cobalt-HSA binding is a clinically useful diagnostic test to rule out myocardial ischemia.
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PMID:A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. 1107 21

Using a dialysis electrode, previous studies showed a clear biphasic release of glutamate during anoxia and ischemia. In this study, we examined two hypotheses: (1) glutamate is of vesicular origin and its release is thus Ca2+- and ATP-dependent in the first phase, while in the second phase glutamate is derived primarily from the metabolic pool, and (2) reversed glutamate uptake, due to electrogenic stoichiometry, produces the second phase during anoxic insult in the rat brain. A dialysis electrode continuously perfused with glutamate oxidase and ferrocene-conjugated bovine serum albumin (BSA) optimized the time resolution of monitoring, allowing quantitative oxygen-independent, real-time measurement of the extracellular glutamate concentration ([Glu]e) during anoxia. [Glu]e dynamics were analyzed during anoxia by combining the dialysis electrode with focal microinjection of substances inducing glutamate release. Following anoxia in the rat brain, a sharp and rapid [Glu]e elevation took place (first phase). The [Glu]e elevation then shifted, continuing a gently sloping rise throughout the anoxic period (second phase). This first phase disappeared with intracranial administration of either Co2+ or omega-conotoxin. The second phase rise increased with focal microinjection of KCl (300 mM, 1 microL) and decreased with NaCl (300 mM, 1 microL), ultimately reaching a plateau in both cases. Preloading with a novel glutamate transporter inhibitor (tPDC) decreased both the first and second phases of [Glu]e elevation. This dialysis electrode system provides data supporting in vivo evidence that the peak of the first phase of [Glu]e elevation is derived from the "neurotransmitter pool," while the second phase is derived from the neuronal and glial "metabolic pool," which is, at least, partly related to a "reversed uptake" mechanism in the anoxic rat brain.
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PMID:Oxygen-independent real-time monitoring of distinct biphasic glutamate release using dialysis electrode in rat striatum during anoxia: in vivo evaluation of glutamate release and reversed uptake. 1110 Dec 12

Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co(2+) to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and (1)H NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co(2+) and Ni(2+). Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.
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PMID:Characterization of the Co(2+) and Ni(2+) binding amino-acid residues of the N-terminus of human albumin. An insight into the mechanism of a new assay for myocardial ischemia. 1112 Nov

PNA+Tempol, albumin containing conjugated (polynitroxyl albumin; PNA) and free (4-hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl; Tempol) nitroxide may protect against injury caused by reactive oxygen species. Therefore, the actions of PNA+Tempol on liver injury and inflammation induced by hepatic ischemia and reperfusion (I/R) were examined. Rats were subjected to 1 h ischemia followed by 24 h reperfusion in the absence (I/R) or presence of PNA+Tempol (25%; 15 mL/kg, i.v.) (I/R+PNA+Tempol) or human serum albumin (23%; 13.5 mL/kg, i.v.) (I/R+HSA). Test solutions were administered prior to and for 2 h during reperfusion. Sham-operated rats underwent surgery with neither ischemia nor infusion. I/R+PNA+Tempol rats had significantly less liver injury and inflammation than I/R rats. I/R+PNA+Tempol livers exhibited focal lesions whereas I/R livers exhibited global necrosis. Likewise, plasma ALT activity was significantly lower in I/R+PNA+Tempol rats. PNA+Tempol reduced I/R-induced neutrophil accumulation and intercellular adhesion molecule-1 (ICAM-1) expression. HSA did not alter I/R-induced liver injury or inflammation. Sham-operated rats exhibited normal liver morphology and no inflammation. Attenuation of I/R liver injury by PNA+Tempol may be mediated by its effect on inflammation, the major contributor to I/R injury. Reduction of inflammation by PNA+Tempol is most likely due to the antioxidative nature of the nitroxides.
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PMID:Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion. 1119 30

The localization of caspase-1 protein, interleukin-1beta (IL-1beta)-converting enzyme, was immunohistochemically examined in the hippocampal CA-1 subfield by a transient occlusion of bilateral common carotid arteries in Mongolian gerbils. Immunoreactivities for caspase-1 were found in microglias, astrocytes, endothelial cells of capillaries and some non-pyramidal neurons. Immunopositive microglias increased in number from 3 days until 7 days from the transient ischemia, and astrocytes also increased in number from 3 days until 28 days. At the electron microscopic level, caspase-1 immunoreaction endproducts were associated with Golgi apparatus in glial cells, endothelial cells of blood vessels and non-pyramidal neurons. The delayed neuronal death of CA-1 pyramidal cells was significantly protected by the treatment of specific caspase-1 inhibitor (Ac-WEHD-CHO) or broad caspase family inhibitor (z-VAD-FMK). Cell death was protected in a dose dependent manner by the former by 43-57%, and by the latter by 66-91% when injected at 1 and 10 microg, respectively. On the other hand, the protective effect of specific caspase-3 inhibitor (Ac-DMQD-CHO) was less significant at higher dose (10 microg) by 33% (P<0.05), and not detectable at lower dose (1 microg) by 13% (P=0.27). Furthermore, a significant decrease of microglias and astrocytes was found in the CA-1 as well as the reduction of IL-1beta and caspase-1 immunoreactivities by the treatment of Ac-WEHD-CHO. Extravasation of serum albumin was also extremely reduced by this treatment. These findings suggest that the inhibition of caspase-1 activity ameliorates the ischemic injury by inhibiting the activity of IL-1beta.
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PMID:Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia. 1122 99


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