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)

The purpose of this study was to validate the Albumin Cobalt Binding (ACB) assay at the Seattle Veterans Affairs (VA) Hospital to determine if it would provide an earlier rule-out of acute coronary syndrome (ACS) in patients, compared to current use of cardiac injury markers. This study compares the distribution of ischemia modified albumin (IMA) values of our patient population to those provided by the kit manufacturer. IMA values were determined photometrically on a Roche Modular Analytical System on 200 subjects: 69 subjects not experiencing chest pain (normals), 78 subjects presenting to the emergency room (ER) with chest pain whose initial and subsequent troponin results were negative (non-converters), and 53 subjects presenting to the ER with chest pain whose initial troponin result was negative but subsequent troponin results were positive (converters). Based on the relationships between IMA values in the initial samples from the non-converters and converters, we constructed a ROC curve to identify an optimum IMA rule-out value. The IMA values (mean+/-SD) for the normals, non-converters, and converters were 89+/-7.1, 100+/-13.9, and 126+/-14.1 U/ml, respectively, and each mean was statistically different from the means of the other groups. The ROC curve comparing converters and non-converters showed an area of 0.89 (p <0.001) compared to the line of identity. An IMA cut-off of 97 U/ml gives a 98% sensitivity and 45% specificity and may be the best decision point to differentiate between these groups in our population. Nine of 78 non-converters were classified as having unstable angina. In conclusion, the ACB assay has a strong negative predictive value and sensitivity in our population for predicting the troponin results at 6 to 24 hr post-presentation. Because ACB results may be facility- and instrument-dependent, each facility should conduct an independent ROC analysis to determine the optimal IMA rule-out level. The ACB assay, when used in conjunction with cardiac injury markers and assessment of unstable angina, holds promise in reducing inappropriate low-risk hospital admissions and improving the clinical management of patients with chest pain.
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PMID:Albumin cobalt binding assay to rule out acute coronary syndrome. 1583 Jul 11

Upregulation of heme oxygenase (HO)-1, a heat shock protein 32, protects against hepatic ischemia/reperfusion (I/R) injury. Activation of "innate" toll-like receptor (TLR) 4 system triggers the I/R injury cascade. This study explores cytoprotective functions of HO-1 overexpression following exogenous administration of cobalt protoporphyrin (CoPP), and its relationship with the TLR4 pathway in a model of mouse partial hepatic warm I/R injury. CoPP treatment markedly improved hepatic function and histology, and suppressed pro-inflammatory cytokine elaboration profile, as compared with untreated controls. Although administration of CoPP did not affect intrahepatic TLR4, it downregulated IFN-inducible protein 10 (IP-10) expression. As IP-10 is the major product of type-1 IFN pathway downstream of TLR4, we then infused recombinant IFN-beta (rIFN-beta) directly into mouse livers. Interestingly, infusion of rIFN-beta upregulated hepatic IP-10 expression. In contrast, adjunctive CoPP treatment decreased IP-10 levels in mouse livers infused with rIFN-beta. Thus, CoPP-induced HO-1 upregulation suppresses type-1 IFN pathway downstream of TLR4 system in hepatic warm I/R injury model.
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PMID:HO-1 upregulation suppresses type 1 IFN pathway in hepatic ischemia/reperfusion injury. 1591 27

Skin flap survival is dependent on an adequate blood supply and on the resistance to ischemia. Experimentally we tested the effect of pharmacological preconditioning on the survival of skin flaps. The survival of an ischemic skin flap (McFarlane flap) was tested using the local application of cobalt gel in three groups of Wistar rats. The mean flap necrosis of the control group was 59.15%. The rats treated by the cobalt gel once a week showed mean necrosis in 39.09%; the rats receiving the application of the cobalt gel three times a week in 26.33%. The treated groups presented with significantly lower flap necrosis in comparison to the untreated controls. There was a significant difference in the flap necrosis occurrence according to the application frequency of the cobalt gel. The expression of the genes involved in angiogenetic processes encoding vascular endothelial growth factor (VEGF) and glycolytic enzymes was influenced in a non-mitochondrial way in this study. The results show that non-mitochondrial preconditioning could prolong the survival of an ischemic flap.
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PMID:Local pharmacological preconditioning increases the survival of experimental skin flaps in rats. 1599 1

The Albumin Cobalt Binding Test is a quantitative in vitro diagnostic test used on human serum that detects ischemia-modified albumin by measuring the cobalt binding capacity of albumin in human serum. Ischemia modified albumin is intended for use in conjunction with ECG and cardiac troponin as an aid to short term risk stratification of patients presenting with chest pain suggestive of cardiac origin. Thus, in patients with chest pain or equivalent symptoms suggestive of cardiac origin, with non-diagnostic ECG and normal troponin, a negative IMA can be used as an aid to rule out acute coronary syndrome (ACS) in low risk patients.
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PMID:[Ischemia-modified albumin: new marker of myocardial ischemia?]. 1601 13

Exposure to moderate hypoxia alone does not cause neuronal death as long as blood pressure and cerebral blood flow are maintained in mammals. In neonatal and adult mammals including rats and mice, carotid occlusion in combination with hypoxia produces neuronal death and brain infarction. However, preexposure to 8% oxygen for 3 h protects the brain and likely other organs of neonatal and adult rats against combined hypoxia-ischemia 24 h later. In this paper, the possible mechanisms of this so-called hypoxia-induced tolerance to ischemia is discussed. One mechanism likely involves hypoxia-inducible factor-1alpha (HIF-1alpha). HIF-1alpha is a transcription factor that - during hypoxia - binds with a second protein (HIF-1beta) in the nucleus to promoter elements in hypoxia-responsive target genes. This causes upregulation of HIF target genes including VEGF, erythropoietin, iNOS, glucose transporter-1, glycolytic enzymes, and many other genes to protect the brain against ischemia 24 h later. In addition, non-HIF pathways including MTF-1, Egr-1 and others act directly or indirectly on other target genes to also promote hypoxia-induced preconditioning. Hypoxia preconditioning can be mimicked by iron chelators like desferrioxamine and transition metals like cobalt chloride that inhibit prolyl hydroxylases, increase HIF-1alpha levels in the brain, and produce protection of the brain against combined hypoxia-ischemia 24 h later. This hypoxia preconditioning has potential clinical usefulness in protecting high-risk newborns or to provide protection prior to surgery.
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PMID:Hypoxia preconditioning in the brain. 1604 41

The measurement of cardiac troponins has emerged as the biochemical "gold standard" for the diagnosis and management of patients with acute chest pain. However, earlier markers should support investigation strategies, as several patients with acute coronary syndrome might present with non-diagnostic concentrations. Ischemia-modified albumin (IMA), measured by the albumin cobalt binding (ACB) assay, was recently proposed for early detection of myocardial ischemia. To establish the potential influence of endurance training on the diagnostic approach to patients with suspected myocardial injury, cardiac troponin T (cTnT), creatine kinase isoenzyme MB (CK-MB), myoglobin and IMA were evaluated in healthy individuals subjected to different aerobic workloads. The concentrations of both IMA and CK-MB were significantly increased in athletes subjected to high-workload endurance training, whereas the concentration of cTnT and myoglobin was not influenced by physical exercise in the medium term. Taken together, our results demonstrate that demanding aerobic physical activity might influence the generation of IMA, which might be increased in the medium term following high-workload endurance training, while the concentration of other conventional markers of myocardial injury remains non-diagnostic.
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PMID:High-workload endurance training may increase serum ischemia-modified albumin concentrations. 1620 35

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.
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PMID:Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration. 1621 53

Brain death (BD) of the donor, a risk factor uniquely relevant for organs derived from cadaver donors, influences organ quality by induction of various inflammatory events. Consequently ischemia/reperfusion injury is deteriorated and acute and chronic rejections accelerated. Donor treatment might be an approach to improve the quality of the graft. The induction of heme oxygenase 1 (HO-1) has been shown to exert beneficial effects in living-donor transplantation models. Therefore, we examined the impact of donor treatment with the selective inducer of HO-1, cobalt protoporphyrin (CoPP), on organ quality and transplant outcome in a standardized BD model in a F344-->LEW kidney transplant rat model. Immediately after BD induction, donor animals were administered a single dose of CoPP (5 mg/kg) and in control groups, HO-1 activity was blocked with zinc protoporphyrin (ZnPP, 20 mg/kg). Recipients of organs from brain-dead donors treated with CoPP survived significantly better than those from untreated brain-dead donors (p < 0.05) and intra-graft analysis showed improved histology (p < 0.05). Blockade of HO-1 with ZnPP decreased the survival rates (p < 0.05) comparable to untreated brain-dead donors. Our results demonstrate that HO-1 induction by one single treatment of CoPP in brain-dead donors leads to enhanced allograft survival.
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PMID:Improved long-term graft survival after HO-1 induction in brain-dead donors. 1646 56

Ischemic preconditioning protects steatotic livers against ischemia-reperfusion (I/R) injury, but just how this is achieved is poorly understood. Here, I/R or preconditioning plus I/R was induced in steatotic and nonsteatotic livers followed by investigating the effect of pharmacological treatments that modulate heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs). MAPKs, HSPs, protein kinase C, and transaminase levels were measured after reperfusion. We report that preconditioning increased HSP72 and heme-oxygenase-1 (HO-1) at 6 and 24 hours of reperfusion, respectively. Unlike nonsteatotic livers, steatotic livers benefited from HSP72 activators (geranylgeranylacetone) throughout reperfusion. This protection seemed attributable to HO-1 induction. In steatotic livers, preconditioning and geranylgeranylacetone treatment (which are responsible for HO-1 induction) increased protein kinase C activity. HO-1 activators (cobalt(III) protoporphyrin IX) protected both liver types. Preconditioning reduced p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in HSP72 induction though HO-1 remained unmodified. Like HSP72, both p38 and JNK appeared not to be crucial in preconditioning, and inhibitors of p38 (SB203580) and JNK (SP600125) were less effective against hepatic injury than HO-1 activators. These results provide new data regarding the mechanisms of preconditioning and may pave the way to the development of new pharmacological strategies in liver surgery.
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PMID:Heat shock proteins and mitogen-activated protein kinases in steatotic livers undergoing ischemia-reperfusion: some answers. 1665 15

The biochemical marker of myocardial ischemia is detected prior to the development of myocardial necrosis, i.e. a novel biochemical evaluation based on human serum albumin binding to cobalt, a transitional metal. The evaluation is known as Albumin Cobalt Binding (ACB) Test. ACB Test is applied to detect the presence of Ischemia Modified Albumin (IMA), an albumin which has altered binding capacity to bind metal ion such as cobalt (Co), copper (Cu) and nickel (Ni) in N-terminus region. It is produced when the serum albumin convenes with ischemic heart tissues. ACB Test detecting the presence of myocardial ischemia that occurs prior to myocardial necrosis has been studied by some researchers and they found an ACB increase prior to troponin increase. The cut off point of ACB evaluation was 85 U/ml. Provided that the value was greater than 85 U/ml then there was positive myocardial ischemia. But it should be noticed that IMA increase in the plasma may be due to other tissues such as gastrointestinal tissues or skeletal muscles tissues. We should also consider other factors which may affect the evaluation result such as severe hypoalbuminemia that will cause a false-high result. ACB Test may be used as an early marker of myocardial ischemia that occurs prior to myocardial necrosis.
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PMID:Albumin cobalt binding (ACB) test: its role as a novel marker of acute coronary syndrome. 1679 11


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