Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human albumin therapy is highly neuroprotective in focal cerebral ischemia. Because albumin is the main carrier of free fatty acids (FFA) in plasma, we investigated the content and composition of plasma FFA in jugular vein (JV), femoral artery (FA) and femoral vein (FV) of rats given intravenous human albumin (1.25 g/kg) or saline vehicle (5 mL/kg) 1 h after a 2 h middle cerebral artery occlusion (MCAo) or sham surgery. Arachidonic acid was the only FFA significantly increased by MCAo in all plasma samples prior to albumin administration, remaining at the same level regardless of subsequent treatments. Albumin treatment induced in both MCAo- and sham-groups a 1.7-fold increase in total plasma FFA (mainly 16:0, 18:1, 18:2n-6) during 90-min reperfusion. MCAo selectively stimulated the albumin-mediated mobilization of n-3 polyunsaturated fatty acids (PUFA), with an early increase in 22:5n-3 and 22:6n-3 in the FA prior to detectable changes in the JV. In the MCAo-albumin group, the lower level of FFA in JV as compared with FA and FV suggests an albumin-mediated systemic mobilization and supply of FFA to the brain, which may favor the replenishment of PUFA lost from cellular membranes during ischemia and/or to serve as an alternative source of energy, thus contributing to albumin neuroprotection.
 ...
PMID:Systemic fatty acid responses to transient focal cerebral ischemia: influence of neuroprotectant therapy with human albumin. 1239 May 13

Recently a new biological marker, Ischemia Modified Albumin (IMA), measured by the Albumin Cobalt Binding (ACB) test, was introduced for detection of myocardial ischemia. During ischemia, the metal binding capacity of albumin for certain transition metals like cobalt is reduced. The precise mechanism of action for producing IMA is not known but appears to be related to the production of reactive oxygen species that modify the metal binding sites. The ACB test is a quantitative assay that detects IMA by measuring the cobalt binding capacity of albumin in human serum. We evaluated the analytical characteristics of the ACB test, and reagent and specimen stability, using the Cobas MIRA Plus instrument. Coefficients of variation for within-run and between-run assays were <4%. No significant interference was observed for concentrations of triglycerides and hemoglobin up to 7 mmol/l and 3.8 g/l, respectively. No interference was apparent with bilirubin. Measures from paired samples of heparinized plasma and serum were not equivalent. The assay is validated for commercial use with serum, therefore our study reported results for serum specimens only. All assays were completed within 5 hours after blood withdrawal. The one-sided upper 95th percentile, calculated for the ACB test in 150 healthy subjects, was 87.00 U/ml. There was no observed difference between men and women or with age. We conclude that the ACB test adapted on the Cobas MIRA Plus analyzer is satisfactory, but strict attention to sample handling procedures is necessary to maintain stability of the analyte.
 ...
PMID:Analytical performance of the Albumin Cobalt Binding (ACB) test on the Cobas MIRA Plus analyzer. 1514 58

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects against ischemia, even when given by intravenous (iv) administration 24 h after stroke. Transport of PACAP across the blood-brain barrier (BBB) by peptide transport system (PTS)-6 underlies its effectiveness after iv administration. However, PACAP transport is modified after central nervous system (CNS) injury, raising the question of whether cytokines or BBB disruption affects PTS-6 activity. Lipopolysaccharide (LPS) is derived from bacterial cell walls and affects the passage of other proteins across the BBB through its release of cytokines and disruption of the BBB. Here, we examined by several methods the transport of radioactively labeled PACAP (I-PACAP) across the BBB after intraperitoneal (ip) injection of LPS. After three doses of LPS, studies at a single time point found a differential effect of LPS on the brain/serum ratio for I-PACAP and radioactively labeled albumin (I-Albumin). Whereas LPS increased the ratio for I-Albumin, demonstrating BBB disruption, it decreased the ratio for I-PACAP. Multiple-time regression analysis, capillary depletion, and brain perfusion showed that this decrease was fully explained by a decrease in the initial, reversible binding of I-PACAP to brain endothelium, while the rate of transport of PACAP into the brain was not altered. These methods also showed that the LPS-treated mice were volume contracted. This volume contraction concentrated the amount of I-PACAP in the blood and so increased the amount of I-PACAP presented to the BBB. Lack of change in transport rate combined with volume contraction resulted in a net increase of about 30% of the iv dose of I-PACAP entering the brain. LPS did not alter the efflux of I-PACAP from the CNS. In conclusion, PTS-6 remains active and should be able to deliver therapeutic amounts of PACAP to the CNS in brain injuries involving cytokine release and BBB disruption.
 ...
PMID:Effect of lipopolysaccharide on the transport of pituitary adenylate cyclase activating polypeptide across the blood-brain barrier. 1558 20

We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin-CK-MB-TnI triad had a sensitivity of 57%. The combination of IMA-myoglobin-CK-MB-TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia.
 ...
PMID:Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting. 1627 Apr 50

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.
 ...
PMID:Albumin cobalt binding assay to rule out acute coronary syndrome. 1583 Jul 11

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.
 ...
PMID:[Ischemia-modified albumin: new marker of myocardial ischemia?]. 1601 13

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.
 ...
PMID:Albumin cobalt binding (ACB) test: its role as a novel marker of acute coronary syndrome. 1679 11

The field of diagnostic cardiac biomarkers has grown exponentially since the development of an assay for aspartate transaminase activity to diagnose myocardial infarction in 1954. The clinician now has a vast array of clinical tools, which include biomarkers of inflammation, ischaemia and necrosis as well as sensitive imaging technology and coronary anatomy intervention at their disposal when evaluating acute coronary syndromes. Previously the World Health Organisation (1979) defined a myocardial infarction (MI) in the presence of two of the following triad: History of chest pain, electrocardiographic (ECG) changes and a rise in cardiac enzymes to twice the upper limit of normal. At this time, creatine kinase and its MB isoenzyme were the preferred biochemical markers. The clinical requirements of early diagnosis, risk stratification and effective treatment have stimulated the development of numerous new and cardiac specific biomarkers (e.g. cardiac troponins). Cardiac troponins are now integral to the diagnosis of MI and have led to the reclassification of MI into either ST elevated MI (STEMI) or non-ST elevated MI (NSTEMI). Subsequent to the release of each new cardiac specific assay there typically follows an array of studies supporting or refuting its efficacy. Many cardiac biomarkers originally proposed with high sensitivity and specificity for ACS are now of questionable clinical value or require the addition of significant caveats once they have been fully evaluated. Indeed, acute exercise often stimulates perturbations in cardiac biomarkers; such as elevations in creatine kinase, cardiac troponins or reductions in Ischemia Modified Albumin (IMA). Such an influence of exercise upon commercially available cardiac biomarkers may hamper or distort the viability of such assays in the clinical arena. The purpose of this review is to examine the influence of exercise upon a number of established and novel cardiac biomarkers, including markers of necrosis, inflammation, cardiac function and ischemia. We will also address the clinical relevance of such exercise-induced perturbations.
 ...
PMID:The influence of exercise upon cardiac biomarkers: a practical guide for clinicians and scientists. 1758 54

Epileptogenesis is common following brain insults such as trauma, ischemia and infection. However, the mechanisms underlying injury-related epileptogenesis remain unknown. Recent studies demonstrated impaired integrity of the blood-brain barrier (BBB) during epileptogenesis. Here we review accumulating experimental evidence supporting the potential involvement of primary BBB lesion in epileptogenesis. Data from animal experiments demonstrate that primary breakdown of the BBB prone animals to develop focal neocortical epilepsy that is followed by neuronal loss and impaired functions. The extravasation of albumin from the circulation into the brain neuropil was found to be sufficient for the induction of epileptogenesis. Albumin binds to transforming growth factor beta receptor 2 (TGFbetaR2) in astrocytes and induces rapid transcriptional modifications, astrocytic transformation and dysfunction. We highlight a novel cascade of events which is initiated by increased BBB permeability, eventually leading to neuronal dysfunction, epilepsy and cell loss. We review potential mechanisms and existing experimental evidence for the important role of astrocytes and the TGFbeta pathway in epileptogenesis. Finally, we review evidence from human clinical data supporting the involvement of BBB lesion in epilepsy. We propose that primary vascular injury, and specifically BBB breakdown and repair, are key elements in altered interactions within the neurovascular unit and thus may serve as new therapeutic targets.
 ...
PMID:Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. 1936 6

Albumin, the principal transporter of plasma fatty acids, binds to majority of the drugs ingested, traps oxygen radicals and has potent anti-oxidant actions. Albumin binds to its specific binding sites on vascular endothelial cells and thus, prevents endothelial apoptosis. Albumin regulates the enzyme pyruvate dehydrogenase, the flux of glucose and lactate in astrocytes, and enhances the formation of anti-inflammatory lipoxins, resolvins and protectins from docosahexaenoic acid (DHA) and other polyunsaturated fatty acids that, in turn, could limit ischemia-induced neuronal damage. This may explain the beneficial action of DHA-enriched albumin in stroke and other critical diseases.
 ...
PMID:Albumin and lipid enriched albumin for the critically ill. 1975 60


<< Previous 1 2 3 4 5 Next >>