OBJECTIVE

Oxidative stress results from an imbalance between the production of free radicals and antioxidant activity. There is wide agreement that patients undergoing regular dialysis treatment experience increased oxidative stress. The aim of this study was to investigate serum total antioxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), and coenzyme Q10 (CoQ10) levels in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, compared with controls.

METHODS

This study was performed on 41 (21 men, 20 women) CAPD patients, 38 (20 men,18 women) HD patients, and 43 (23 men, 20 women) healthy control subjects. CoQ10 levels were standardized using blood lipids.

RESULTS

Serum TAS levels and CoQ10/total cholesterol values of the HD and CAPD patients were significantly lower, whereas serum IMA and TOS levels were significantly higher, than those of controls. Furthermore, CoQ10/LDL, CoQ10/triglycerides, and CoQ10/total cholesterol + triglycerides values of the CAPD patients were significantly lower than those of controls. No differences were found between serum IMA, TAS, TOS, CoQ10 levels, and adjusted CoQ10 values of the CAPD and HD patients.

CONCLUSIONS

Our results suggest that oxidative stress is increased in HD and CAPD patients compared with controls, as proven by decreased TAS and adjusted CoQ10 levels and increased TOS and IMA levels. Therefore, an antioxidant supplementation to these patients may be suggested.

Laparotomy remains the gold standard for diagnosis of acute mesenteric ischemia (AMI), but is often unhelpful or too late due to non-specific clinical and radiological signs. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of the novel serological biomarkers intestinal fatty acid-binding protein (I-FABP), α-glutathione S-transferase (α-GST), D-lactate, ischemia modified albumin (IMA), and citrulline to detect AMI. A systematic search of electronic databases was performed to identify all published diagnostic accuracy studies on I-FABP, α-GST, D-lactate, IMA, and citrulline. Articles were selected based on pre-defined inclusion and exclusion criteria. Risk of bias and applicability were assessed. Two-by-two contingency tables were constructed to calculate accuracy standards. Summary estimates were computed using random-effects models. The search yielded 1925 papers, 21 were included in the final analysis. Pooled sensitivity and specificity for investigated biomarkers were: I-FABP (Uden); 79.0 (95% CI 66.5-88.5) and 91.3 (87.0-94.6), I-FABP (Osaka); 75.0 (67.9-81.2) and 79.2 (76.2-82.0), D-lactate; 71.7 (58.6-82.5) and 74.2 (69.0-79.0), α-GST; 67.8 (54.2-79.5) and 84.2 (75.3-90.9), IMA; 94.7 (74.0-99.9) and 86.4 (65.1-97.1), respectively. One study investigated accuracy standards for citrulline: sensitivity 39% and specificity 100%. The novel serological biomarkers I-FABP, α-GST, IMA, and citrulline may offer improved diagnostic accuracy of acute mesenteric ischemia; however, further research is required to specify threshold values and accuracy standards for different aetiological forms.

New blood vessel formation is a critical requirement for treating many vascular and ischemia related diseases, as well as for many tissue engineering applications. Angiogenesis and vasculogenesis, in fact, represent crucial processes for the functional regeneration of complex tissues through tissue engineering strategies. Several growth factors (GFs) and signaling molecules involved in blood vessels formation have been identified, but their application to the clinical setting is still strongly limited by their extremely short half-life in the body. To overcome these limitations, we have developed a new injectable controlled release device based on polymeric nanoparticles for the delivery of two natural proangiogenic GFs: platelet derived growth factor (PDGF-BB) and fibroblast growth factor (FGF-2). The nanoparticle system was prepared by a modified solvent diffusion technique, encapsulating the GF both in presence and in the absence of two stabilizing agents: bovine serum albumin (BSA) and heparin sodium salt (Hp). The developed nanocarriers were characterized for morphology, size, encapsulation efficiency, release kinetics in vitro and GF activity in cell cultures. The results have indicated that the coencapsulation of stabilizing agents can preserve the GF active structure and, in addition, increase their encapsulation efficiency into nanoparticles. Through this optimization process, we were able to raise the encapsulation efficiency of FGF-2 to 63%, and that of PDGF-BB to 87%. These PLGA:poloxamer blend nanoparticles loaded with GFs were able to release PDGF-BB and FGF-2 in a sustained fashion for more than a month. This work also confirms other positive features of PLGA:poloxamer nanoparticles. Namely, they are able to maintain their stability in simulated biological medium, and they are also nontoxic to cell culture models. Incubation of nanoparticles loaded with FGF-2 or PDGF-BB with endothelial cell culture models has confirmed that GFs are released in a bioactive form. Altogether, these results underline the interest of PLGA:poloxamer nanoparticles for the controlled delivery of GFs and substantiate their potential for the treatment of ischemic diseases and for tissue engineering applications.

Chronic kidney disease (CKD) is highly prevalent, with increasing numbers of patients affected by the disease world-wide, and anemia is a common finding in patients with CKD. Anemia impacts negatively on cardiovascular disease, exercise capacity, and quality of life, resulting in significant mortality and morbidity. The aim of this study was to evaluate the levels of ischemia-modified albumin and lactate in patients with established anemia associated with CKD and its correlations with hemoglobin levels. Hematocrit, hemoglobin, iron, ferritin, albumin, creatinine, lactate, and ischemia-modified albumin (IMA) were measured in 17 patients with established anemia associated to CKD and 19 controls by standard methods. The results of hematocrit, hemoglobin, iron, and albumin were lower in the anemia group than in the control group. Ferritin, creatinine, and lactate levels were higher in anemia of the CKD group than the control group. IMA increase in the anemia group (0.8115+/-0.1304 absorbance units [ABSU]) compared to control (0.4951+/-0.0393 ABSU). Significant correlations between IMA and lactate, IMA and hemoglobin, IMA and creatinine, and hemoglobin and lactate were observed. IMA and lactate increase during anemia and this elevation could be associated to hypoxia due to low hemoglobin levels. However, our data suggest that lactate is more sensitive to anemia compared to IMA.

BACKGROUND

Novel biomarkers of myocardial ischemia and inflammatory processes have the potential to improve diagnostic accuracy of acute coronary syndrome (ACS) within a shorter time interval after symptom onset.

OBJECTIVE

The objective was to review the recent literature and evaluate the evidence for use of novel biomarkers in diagnosing ACS in patients presenting with chest pain or symptoms suggestive of cardiac ischemia to the emergency department or chest pain unit.

METHODS

A literature search was performed in MEDLINE, EMBASE, Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED for studies from 2004 to 2010. We used the inclusion criteria: (1) human subjects, (2) peer-reviewed articles, (3) enrolled patients with ACS, acute myocardial infarction or undifferentiated signs and symptoms suggestive of ACS, and (4) English language or translated manuscripts. Two reviewers conducted a hierarchical selection and assessment using a scale developed by the International Liaison Committee on Resuscitation.

RESULTS

Out of a total 3194 citations, 58 articles evaluating 37 novel biomarkers were included for final review. Forty-one studies did not support the use of their respective biomarkers. Seventeen studies supported the use of 5 biomarkers, particularly when combined with cardiac-specific troponin: heart fatty acid-binding protein, ischemia-modified albumin, B-type natriuretic peptide, copeptin, and matrix metalloproteinase-9.

CONCLUSIONS

In patients presenting to the emergency department with chest pain or symptoms suggestive of cardiac ischemia, there is inadequate evidence to suggest the routine testing of novel biomarkers in isolation. However, several novel biomarkers have the potential to improve the sensitivity of diagnosing ACS when combined with cardiac-specific troponin.

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis and subsequent cardiac remodelling. Cardiac biomarkers can be used for diagnosis and assessment of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The challenges with potential ischaemia markers are specificity and the diagnostic reference standard for assessment. To date, only one, ischaemia modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, has become the diagnostic standard as the biomarker of myocardial necrosis. The sensitive nature of troponin measurement has also revealed that myocardial necrosis is also found in a range of other clinical situations. This illustrates the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B type natriuretic peptides can be shown to be diagnostic and prognostic for both acute ACS and detecting the sequelae of post infarction myocardial insufficiency. The role of the B type natriuretic peptides in detection of cardiac failure, acute and chronic, is well defined. Their role in ACS remains the subject of further studies.

BACKGROUND

Oligodendrocytes need iron in processes of energy generation and myelination. However, excessive levels of iron may exert iron induced oxidative stress and thus lead to tissue degeneration. Monitoring oxidative stress will be of paramount importance in follow-up of patients with many diseases including multiple sclerosis (MS). The aim of this study was to measure total anti-oxidative status (TAS), total oxidative status (TOS) and ischemia modified albumin (IMA) in stable relapse remitting MS (RRMS) patients.

METHODS

Thirty-five RRMS patients (15 males and 20 females; median age 42 (20-55) years) and thirty-five age-sex matched healthy controls (13 males and 22 females; median age 37 (21-60) years) were included in this study. All patients were diagnosed with MS according to the criteria of McDonald.

RESULTS

IMA levels were significantly higher in RRMS patients (P < 0.001), while TAS and TOS did not show any significant difference between groups (P = 0.870 and P = 0.460, respectively).

CONCLUSIONS

Our results suggest IMA as a more efficient serum marker than TAS and TOS in detecting the oxidative stress in MS patients. Serum oxidative stress markers should be included in future study protocols besides clinical and radiological parameters.

OBJECTIVE

To establish the correlation between ischemia-modified albumin (IMA) and malondialdehyde (MDA) and the development of diabetic retinopathy (DRP) in patients with diabetes mellitus.

METHODS

Seventy Type 2 diabetic patients, 35 with DRP, and 36 healthy controls were enrolled in this study. Serum IMA and MDA levels were compared statistically. Receiver operating characteristic curve analysis was also performed to calculate the value of IMA and MDA in distinguishing DRP.

RESULTS

Mean serum IMA levels were 0.658 ± 0.128 absorbance units in the non-DRP group, compared with 0.767 ± 0.074 absorbance units in the DRP group and 0.619 ± 0.044 absorbance units in the control group. Mean serum MDA levels were 0.325 ± 0.172 nmol/mL, 0.244 ± 0.152 nmol/mL, and 0.178 ± 0.131 nmol/mL, respectively. The differences in IMA and MDA levels were statistically significant for all groups (P < 0.05 for all). The areas under the receiver operating characteristic curves for the determination of DRP in diabetic patients were 0.789 (95% confidence interval, 0.682-0.896) for IMA and 0.3 (95% confidence interval, 0.175-0.426) for MDA.

CONCLUSIONS

Both serum IMA and serum MDA levels were higher in the diabetic patients compared with the control group. In particular, the high sensitivity of IMA toward DRP showed that it reflected retinal vascular complication better than MDA. Ischemia-modified albumin may be a useful marker in monitoring the risk of DRP development.

BACKGROUND

Ischemia-modified albumin (IMA), measured by the cobalt-binding capacity of albumin, is a promising biomarker for cardiac ischemia. The IMA-to-serum albumin ratio (IMAR) has been reported to relate to the severity of decompensated liver cirrhosis. This study aimed to assess IMA and IMAR as a liver function test and to investigate whether albumin infusion changes IMAR in patients with liver cirrhosis.

METHODS

Blood samples were collected from healthy volunteers (n=51) and patients with chronic hepatitis (n=25), liver cirrhosis (n=24) and uremia (n=13). Parameters examined included serum levels of IMA, albumin, total bilirubin, creatinine, international normalized ratio (INR), model for end-stage liver disease (MELD) score, child-turcotte-pugh (CTP) score, indocyanine green (ICG) retention rate and total antioxidant capacity (TAC). Paired serum samples from patients pre- and post-albumin infusion (n=9) were collected and the changes were compared.

RESULTS

IMA and IMAR increased in patients with chronic hepatitis or cirrhosis, as compared to healthy volunteers. In patients with liver disease, IMA and IMAR were significantly associated with ICG retention, bilirubin, TAC and INR. In addition, IMAR was associated with CTP and MELD score in patients with cirrhosis. Albumin therapy improved patients' serum levels of creatinine and bilirubin and MELD score, but not IMA and IMAR.

CONCLUSIONS

IMAR, reflecting liver function and oxidative stress, is a more objective liver function test as it was not affected after a 3-day albumin infusion. More investigations, however, are needed to validate the use of IMAR in cases of chronic liver disease.

The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE's importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo. Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA). Methods: A multimodal tracer (64Cu-Rho-G4-CML) was developed using a generation-4 (G4) polyamidoamine (PAMAM) dendrimer, conjugated with both rhodamine and copper-64 (64Cu) chelator (NOTA) for optical and PET imaging, respectively. First, 64Cu-Rho-G4-CML and its non-targeted analogue (64Cu-Rho-G4-HSA) were evaluated chemically using techniques such as dynamic light scattering (DLS), electron microscopy and nuclear magnetic resonance (NMR). The tracers' binding capabilities were examined at the cellular level and optimized using live and fixed HUVEC cells grown in 5.5-30 mM glucose, followed by in vivo PET-CT imaging, where the probes' kinetics, biodistribution, and RAGE targeting properties were examined in a murine model of hindlimb ischemia. Finally, histological assessment of RAGE levels in both ischemic and non-ischemic tissues was performed. Conclusions: Our RAGE-targeted probe demonstrated an average size of 450 nm, a Kd of 340-390 nM, rapid blood clearance, and a 3.4 times greater PET uptake in ischemic RAGE-expressing hindlimbs than their non-ischemic counterpart. We successfully demonstrated increased RAGE expression in a murine model of hindlimb ischemia and the feasibility for non-invasive examination of cellular, tissue, and whole-body RAGE levels with a molecularly targeted tracer.

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.

BACKGROUND

The aim of the present study was to determine the systemic levels of oxidative stress markers, such as ischemia-modified albumin (IMA), advanced oxidation protein products (AOPP), ferric reducing antioxidant power (FRAP) and the prooxidant-antioxidant balance (PAB), to clarify protein redox homeostasis in patients with Alzheimer's disease, and to compare them with mentally healthy persons of the same age.

METHODS

A total of 38 patients with Alzheimer's disease (AD) and 34 sex- and age-matched mentally healthy control subjects were included in this study.

RESULTS

The patients had significantly higher AOPP, IMA and PAB in the patient group than in the control group (P = 0.004, P = 0.001, P = 0.007, respectively). The FRAP was significantly lower in the patients with AD than in the control subjects (P = 0.002), and according to the receiver operating characteristic curves, the IMA and AOPP areas are below the 0.700 receiver operating characteristic curve line (area under the curve 0.817 and 0.730, respectively; 95% CI 0.709-0.898 and 0.612-0.828, respectively).

CONCLUSIONS

Increased IMA, AOPP and PAB, and decreased FRAP are likely to be results of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive oxygen species in AD. The IMA could be used for the better evaluation of clinical status, as well as the independent characteristic symptoms of AD, for the purposes of routine clinical laboratory analysis.

BACKGROUND

We investigated the ischemia-modified albumin (IMA), advanced oxidation protein products (AOPPs), prooxidants-antioxidants balance (PAB), and ferric reducing antioxidant power (FRAP) concentrations in patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) and compared the results to those of normoglycemic individuals at baseline and 2 hours after glucose loading.

METHODS

An oral glucose tolerance test was performed on age-matched subjects (n = 110) with a body mass index (BMI) < 27 kg/m(2). Subjects were categorized as normoglycemic (n = 35), IFG (n = 25), IGT (n = 30) and DM (n = 20) according to the WHO criteria. The IMA, AOPP, PAB, FRAP concentrations were determined by colorimetric methods.

RESULTS

At baseline, the AOPP concentrations were significantly higher in subjects with IFG and DM compared to normoglycemic subjects (p < 0.01 for all cases). The IFG, IGT and DM patients had a significantly higher IMA at baseline when compared with the normoglycemic individuals (p < 0.001 for all cases). The IMA in IFG subjects was significantly elevated (p < 0.05), while in DM patients, the IMA was significantly decreased (p < 0.001) after glucose loading with respect to baseline concentrations. Following glucose loading, the PAB was significantly decreased from baseline concentrations in normoglycemic individuals (p < 0.001) and in the IFG (p < 0.001) and IGT (p < 0.001) patients.

CONCLUSIONS

In subjects with impaired glucose metabolism, the hyperglycemia is associated with increased IMA, AOPP and PAB concentrations. Increased IMA in subjects with IFG and decreased FRAP concentrations in subjects with IGT after glucose loading suggests that an increase in glucose concentrations can lead to tissue damage by increasing oxidative stress.

Oxidative stress results from either overproduction of free radicals or insufficiency of several anti-oxidant defense systems. It leads to oxidation of main cellular macromolecules and a resultant molecular dysfunction. Thyroid hormones regulate oxidative metabolism and, thus, play a role in free radical production. Studies evaluating oxidative stress in patients with hypothyroidism and hyperthyroidism have been encountered in recent years; however, oxidative status in patients with euthyroid autoimmune thyroiditis (AIT) was not investigated previously. Thirty-five subjects with euthyroid AIT and 35 healthy controls were enrolled in the study. Serum oxidative status was determined by the measurement of total anti-oxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), and oxidized-low density lipoprotein (ox-LDL) levels. Serum TAS levels were significantly lower (p<0.001), while serum TOS levels and IMA levels were significantly higher (p<0.001 and p=0.020, respectively) in patients compared to controls. In both groups, ox-LDL levels were similar (p=0.608). Serum TAS levels were negatively correlated with anti-thyroid peroxidase and anti-thyroglobulin (anti-TG) levels (rho=-0.415, p=0.001 and rho=-0.484, p<0.001, respectively). Serum TOS was positively correlated with anti-TG levels (rho=0.547, p<0.001). Further, TAS was positively correlated with free T4 levels (r=0.279, p=0.043). No correlation was observed between thyrotropin, free T3 levels, and TOS and TAS levels. These results suggest that oxidants are increased, and anti-oxidants are decreased in patients with euthyroid AIT, and oxidative/anti-oxidative balance is shifted to the oxidative side. Increased oxidative stress might have a role in thyroid autoimmunity.

OBJECTIVE

Ischemia-modified albumin (IMA), a new serum biomarker of myocardial ischemia, has been introduced in the diagnosis of acute coronary syndrome. However, few studies have been carried out in patients with stable coronary atherosclerotic heart disease (CHD). We aimed to evaluate the value of IMA in the diagnosis of stable CHD and to determine the correlation between IMA levels and the severity of myocardial ischemia.

METHODS

A total of 129 patients with diagnosed CHD who had signed an informed consent form were enrolled. Patients were willing to undergo coronary angiography, which was the gold standard for the diagnosis of CHD. IMA was detected by the albumin cobalt binding test before coronary angiography.

RESULTS

The mean IMA level of the non-CHD group was 67.68 ± 29.61 U/ml and that of the CHD group was 90.24 ± 29.61 U/ml. In the CHD group, the mean IMA levels of the one-branch lesion group, the two-branch lesion group, and the three-branch lesion group were 79.87 ± 18.37, 98.10 ± 23.39, and 98.06 ± 33.47 U/ml, respectively. IMA levels and the number of diseased coronary arteries were significantly correlated (P<0.01, r=0.299). When the cut-off threshold derived from the receiver operating characteristics curve was determined to be 93.07 U/ml, the sensitivity of admission IMA for a final diagnosis of CHD was 0.49, the specificity was 0.90, the negative predictive value was 0.45, and the positive predictive value was 0.91. Logistic regression analysis showed that IMA (P=0.000, b=2.056, odds ratio=7.815) was an independent predictor of CHD.

CONCLUSIONS

IMA showed a high specificity and predictive value in the diagnosis of CHD. In addition, IMA was a strong and independent predictor of CHD. IMA levels and the number of diseased coronary arteries were significantly correlated.

The results in this study confirm and expand previous reports that ischemia-modified albumin (IMA) is an early marker of ischemia in the setting of percutaneous coronary intervention (PCI). We observed that IMA levels are related to the number of inflations, inflation pressure, and duration of inflations. It is therefore likely that IMA reflects the magnitude and duration of ischemia induced during PCI.

The mechanisms of the complement-mediated myocardial injury associated with ischemia and reperfusion have not been elucidated fully. Complement activation may directly mediate injury through actions of the anaphylatoxins C3a and C5a or generation of the membrane attack complex C5b-9. A model was developed to examine the direct effects of complement activation on heart function, assess myocardial tissue damage, and determine which complement components mediate tissue injury. Isolated rabbit hearts were perfused with Krebs-Henseleit buffer by using a modified Langendorff apparatus. Human plasma was added to the perfusate as a source of complement. Rabbit tissue activates human complement. Treatment with 6% normal plasma resulted in complement activation as assessed by the generation of Bb, C3a, C5a, and SC5b-9. Functional changes in cardiac performance became apparent 7-15 minutes after plasma addition and developed fully over the next 20-30 minutes. The effects were dependent on the complement titer and included 1) an increase in the end-diastolic pressure, 2) a decrease in the developed pressure, 3) an increase in the coronary perfusion pressure, and 4) an increase in lymphatic fluid formation. These effects were not elicited when an inhibitor of complement activation (FUT-175) was present or when heat-inactivated plasma was used. The effects of complement activation on myocardial function could not be reproduced by treatment with recombinant human C5a, zymosan-activated plasma, or plasma selectively depleted of C8. Myocardial tissue accumulated sodium and calcium and lost potassium as a result of complement activation. Activation caused the release of creatine kinase from myocytes and an increase in the radiolabeled albumin space of the hearts. The data demonstrate that complement activation caused decrements in myocardial function and increased the coronary perfusion pressure and lymphatic fluid flow rate. The effects were not mediated by the anaphylatoxins but were dependent on the distal complement component C8, suggesting that C5b-9 was responsible for the physiological changes. Complement activation directly mediated tissue injury in a manner consistent with plasmalemmal disruption as a result of C5b-9 formation. The data suggest that the C5b-9 complex, which is known to form under conditions of ischemia, may contribute directly to myocardial cell injury.

BACKGROUND

Ischemia-modified albumin (IMA) has been suggested as a marker of cardiac ischemia. Little, however, is known about its capacity to predict short-term serious cardiac outcomes (death, myocardial infarction, congestive heart failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients arriving at the emergency department with symptoms that may indicate cardiac ischemia.

METHODS

We screened 546 patients over a 4-week period, of whom 189 fulfilled our entry criteria by presenting to an emergency department with potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an emergency physician who chose to order a troponin I test, and having no serious cardiac outcome before the troponin result became available. We followed the study patients for 72 hours to determine if any experienced a serious cardiac outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting serious cardiac outcomes that could not be diagnosed at presentation with current techniques.

RESULTS

Of the 189 patients, 24 had a serious cardiac outcome within 72 hours after their arrival at the emergency department. The likelihood ratios for IMA measurement within 6 hours after chest pain predicting a serious cardiac outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315-5.79) for IMA < or = 80 U/mL and 0.98 (95% CI 0.86- 1.11) for IMA>> 80 U/mL.

CONCLUSIONS

These data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.

BACKGROUND

Ischaemia-modified albumin (IMA) is increased in diseases associated with oxidative stress, as detected using the albumin cobalt-binding test. Oxidative stress plays an important role in the development of psoriasis.

OBJECTIVE

To investigate circulating IMA levels in patients with psoriasis and its association with the disease characteristics.

METHODS

Serum IMA and albumin concentrations were evaluated in 26 patients with psoriasis and 26 healthy controls matched for age, gender and body mass index. Levels of albumin, IMA and adjusted IMA were compared between the groups.

RESULTS

IMA and adjusted IMA were significantly higher in patients with psoriasis [0.55 ± 0.04 and 0.54 ± 0.05 absorbance units (ABSU), respectively] than in healthy controls (0.38 ± 0.04 and 0.38 ± 0.05 ABSU, respectively). The two groups had similar albumin levels, but there was a negative correlation between IMA and albumin levels in patients with psoriasis. IMA did not correlate with any disease characteristics.

CONCLUSIONS

IMA levels are higher in patients with psoriasis than in healthy controls. IMA might be produced through an adaptive response to chronic hypoxia and oxidative stress, which might play a role in the systemic inflammation seen in psoriasis.

OBJECTIVE

The objective of the study was to quantify markers of myometrial ischemia, necrosis, and inflammation in women undergoing uterine artery embolization (UAE).

METHODS

Women with symptomatic fibroids were randomized to treatment with UAE (n = 14) or abdominal myomectomy (n = 11). Peripheral venous blood samples were taken before and after the procedure, at 24 hours and 6 weeks. Creatine kinase (CK) and ischemia-modified albumin (IMA) were measured as markers of necrosis and ischemia. Inflammation was assessed by measurement of C-reactive protein (CRP).

METHODS

Changes in the markers following UAE and myomectomy were measured.

RESULTS

Following UAE, no change was seen in CK or IMA, but CRP was raised only at 6 weeks. At 24 hours after myomectomy, there were significant rises in all 3 markers, with a return to normal by 6 weeks.

CONCLUSIONS

No significant ischemia or necrosis occurs in the myometrium following UAE, whereas the delayed rise in CRP is likely to reflect necrosis in fibroids.

Ischemia modified albumin (IMA) is a relatively new marker for evaluating patients with cardiac ischemia. Data are emerging on its potential role in non-cardiac ischemic events. In this pilot study we evaluated the utility of IMA in diagnosing acute coronary syndromes (ACS), assessed its role in the diagnosis of non-cardiac ischemia, and correlated its efficacy with troponin T (TnT). Serum levels of IMA were measured in 89 sequential patients who presented to the emergency room with chest pain for which serum TnT was ordered. The patients were classified into 4 groups based on their IMA and TnT results and discharge diagnoses. The data were analyzed with Fischer's exact test. Multivariate logistic regression analysis relating acute coronary syndrome (ACS) to the combination of TnT and IMA was also performed. The results showed that IMA was a useful marker for the diagnosis of ACS. There was a significant relationship between TnT and IMA (p = 0.032), suggesting that both these biomarkers added significant information about the presence of ACS (p = 0.028) and may be useful for triage of patients who present to the emergency room with chest pain. Serum IMA was also increased in a small proportion of patients with symptoms of stroke, suggesting that it should be considered a marker of acute ischemic events and not specific for cardiac ischemia.

BACKGROUND

Acute lung reperfusion injury (ALI) frequently follows an ischemic event in another organ, such as organ transplantation. We recently demonstrated that lung priming with N-acetyl-L-cysteine (NAC) prevented liver ischemia-reperfusion (IR)-induced ALI pending on reduced glutathione (GSH) amount of replenishment. We now assessed the therapeutic effect of NAC-in preventing ALI caused by liver IR-if administered to the lung during liver reperfusion.

METHODS

Rat isolated livers were stabilized (30 min) and then perfused with modified Krebs-Henseleit solution (control, n=20) or made globally ischemic (IR, n=20) for 2 hr. Rat lungs were isolated separately, ventilated, and stabilized (30 min) with Krebs plus 5% bovine albumin. Pairs of liver and lung were then reperfused together for 15 min, followed by only lung recirculation with the liver effluent for another 45 min. Three more controls (n=20 each) and three ischemic groups (n=20 each) included lungs which were treated with 100, 150 or 225 mg x kg(-1) NAC (0.5, 0.74, or 1.1 mmol, respectively) during the 15-min liver and lung reperfusion period.

RESULTS

Pulmonary artery and ventilatory pressures and vascular resistance increased by 60-80% of baseline, compliance decreased, and bronchoalveolar lavage volume and content were abnormally high in the IR-nontreated and the IR-100 lungs. Most parameters in IR-150 and IR-225 lungs remained almost similar to controls. Postinsult GSH content in IR-100, -150, and -225 lungs was at 20%, 110%, and 90% above the IR-nontreated lungs, respectively.

CONCLUSIONS

Lung treatment with NAC during its reperfusion with IR liver effluent prevented ALI. Lung GSH replenishment accounted for lung protection, but its content did not correlate directly with grade of protection; NAC itself seemingly afforded lung protection as well.

OBJECTIVE

There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis.

METHODS

We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing.

RESULTS

Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p<0.05; NT-pro ANP 732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p<0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects.

CONCLUSIONS

The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoked ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.