To improve prognosis in acute coronary syndrome, new clinical applications in terms of diagnosis, risk stratification, and treatment strategies are still under investigation. Ischemia-modified albumin was one of the novel markers of myocardial ischemia. In our study, we aimed to determine the prognostic significance of the albumin cobalt binding capacity test in patients with acute coronary syndromes. We compared the ischemia-modified albumin levels of patients with acute coronary syndrome with those of patients with stable coronary artery disease and those of normal individuals and found them to be significantly higher in the first group (P<0.05). A cutoff value of ischemia-modified albumin of 477 U/ml was found by using receiver operating characteristic curve analysis. Mortality in groups of patients whose ischemia-modified albumin levels were above 477 U (50%) was found to be significantly higher than in those whose levels were below 477 U (8.3%) (P<0.05). The sensitivity and specificity of the cutoff value, 477 U/ml, for the 1-year mortality were found to be 70 and 82%, respectively. Using the Cox regression model the relation of albumin cobalt binding capacity test results with mortality was statistically significant (beta=1.013, confidence interval 95%, P=0.01) and independent of the existence of hypertension, diabetes, and advanced age. In conclusion, ischemia-modified albumin was found to be significantly related to 1-year mortality. Prognostic significance of ischemia-modified albumin should be evaluated in large populated and randomized study groups. Afterwards, ischemia-modified albumin could be used in risk stratification modality in patients with acute coronary syndrome.

BACKGROUND

Thyroid disorders especially hypothyroidism is associated with increased generation of oxidants. Nitric oxide and ischemia modified albumin are considered markers for oxidative stress. In addition, nitric oxide is involved in regulation of thyroid function and coagulation profile alteration in thyroid disorders may produce ischemia like conditions.

METHODS

Nitric oxide and ischemia modified albumin were estimated in fifty patients of newly diagnosed hypothyroidism using standard photocolorimetric techniques. Results were compared with fifty healthy euthyroid controls and subjected to appropriate statistical analysis.

RESULTS

Nitric oxide and ischemia modified albumin were found to be significantly raised (p < 0.05) in hypothyroid patients as compared to controls. A positive, but statistically insignificant correlation was observed between nitric oxide and ischemia modified albumin.

CONCLUSIONS

Estmation of nitric oxide and ischemia modified albumin in hypothyroidism may help to throw light on its pathogenesis and assessing the severity of the disease, though further research is needed to establish their role as biomarkers in hypothyroidism.

OBJECTIVE

To determine whether a biological marker of ischemia, ischemia-modified albumin (IMA), alone or normalized to albumin serum concentration, was modified during the course of pregnancy and so could be used for discrimination between normal pregnancy and preeclampsia.

METHODS

Serum IMA concentrations and IMA to serum albumin ratio (IMA/alb) were compared in 22 nonpregnant healthy women (NP), 19 healthy pregnant women (HP) and 20 pre-eclamptic women (PE). Influence of age of gestation on these markers was also investigated.

RESULTS

IMA to albumin ratio (IMA/alb) was significantly increased in HP compared with NP (IMA/alb. HP: 2.60 +/- 0.38 kU/g and IMA/alb. NP: 2.10 +/- 0.22 kU/g; p < 0.05). Both IMA and IMA/alb were significantly elevated during PE compared with HP (IMA HP: 98.4 +/- 9.2 kU/l and IMA PE 116.9 +/- 12.3 kU/l, p < 0.001; IMA/alb HP: 2.60 +/- 0.38 kU/g and IMA/alb PE: 3.79 +/- 0.75 kU/g p < 0.001)). Both IMA and IMA/alb were increased in PE up to delivery. No correlation could be demonstrated between gestational age and maternal IMA both in HP (r = 0.13; p = 0.071) or PE (r = 0.05; p = 0.318).

CONCLUSIONS

IMA and IMA normalized to albumin appear to be significantly increased during pathological pregnancies. These results confirm that IMA could be used as a biological marker of preeclampsia. These data need to be confirmed by determining intra-individual IMA change during normal and pathological pregnancy.

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.

Considerable effort by clinicians and scientists focuses on the utility of biomarkers to prevent, diagnose and manage adverse cardiac events as well as provide information on a specific patient's underlying pathology. Although troponins I and T (TnI and TnT) are cardiac specific markers that yield diagnostic and prognostic value in patients with myocardial injury, troponins cannot be utilized in all clinical settings. Troponins have limited utility for the diagnosis of early ischemia and preoperative myocardial infarction. Troponin T also lacks specificity in patients with renal failure. New markers, such as ischemia modified albumin (IMA) and CD40 ligand, and new technologies, such as proteomics, are under investigation to advance our knowledge of heart disease.

Ischemia-modified albumin (IMA), measured with the albumin cobalt binding test, is a marker of myocardial ischemia. We measured IMA concentrations after elective direct-current cardioversion for atrial fibrillation to determine whether transient myocardial ischemia occurs. Patients with electrocardiographic changes after cardioversion (ST-depression and/or T-wave inversion) had significantly higher IMA levels than those without these changes. Thus, elevated levels of IMA after cardioversion may reflect transient myocardial ischemia.

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.

BACKGROUND

In the past few years ischemia modified albumin (IMA) has emerged as a new biomarker of ischemia in the area of monitoring acute coronary syndromes. We hypothesized that reduced blood flow, such as that resulting from vascular compression in complicated labors or placental ischemia, may increase IMA. IMA level in cord blood could then serve as an indicator of fetal hypoxia and fetal tissue ischemia and serve as a biomarker of the severity of these conditions.

METHODS

We performed a case-control study with 26 newborns (12 normal term deliveries, Apgar 8-9; and 14 complicated labors or pre-term deliveries, Apgar 5-8). Complications were: prematurity (3), fetal distress (6), premature rupture of membranes (6), intrauterine growth retardation (3), pre-eclampsia (1). We also studied 30 healthy adults. IMA was measured in serum from cord blood (or venous blood for adults) by the decrease in cobalt 2+ binding.

RESULTS

IMA levels in neonates from non-complicated deliveries are significantly higher (45%, p < 0.005) than those of an adult control population, suggesting that IMA may increase as a consequence of labor. This increased IMA in neonates could not be accounted for by the changes in albumin concentration. It is conceivable that a transient increase in IMA reflects, in part, transient localized tissue ischemia due to the external forces exerted on the fetus during the mechanism of labor. IMA levels in cord blood from neonates from complicated deliveries are 50% higher than in neonates from uneventful deliveries (p < 0.05) while their albumin values are not significantly different (32 +/- 3 vs. 33 +/- 2 g/l). Moreover, IMA seems to be responsive to hypoxic fetal distress, showing values more than 300% higher in cases of severe fetal hypoxia (Apgar 5 n = 2: 2.19 +/- 0.01 AU vs. 0.64 +/- 0.24 for controls). IMA values did not correlate significantly with either lipoperoxides or CRP levels.

CONCLUSIONS

This is the initial reporting of IMA levels in cord blood from normal deliveries compared to healthy adult ranges and neonates from complicated deliveries. Cord blood IMA levels may be an indicator of fetal ischemia and/or hypoxia. This test could become an additional biomarker to be used in conjunction with other markers and/or clinical scores aimed at determining risk of neurological complications of fetal distress.

Recent studies have suggested that heart-type fatty acid-binding protein (H-FABP) may detect ongoing myocardial damage involved in the progression of acute coronary syndromes (ACS). This study was prospectively designed to examine whether the combination of H-FABP, a marker for ongoing myocardial damage, and ischemia-modified albumin (IMA), a marker for myocardial ischemia, would effectively diagnose patients with ACS. H-FABP values above 1.5 microg/l can be correctly measured via an ELISA and 6 microg/l is the currently used cut-off value (1-3). We measured serum H-FABP and IMA of 108 patients on admission within 12 hr after onset of chest pain and normal troponin T. serum samples from ACS group (n=82) had decreased capacity of ACB [64 (61-67) U/ml] compared with non-ACS ischemic chest pain group (n=26) samples [75 (71-78) U/ml] (P<0.05). The combination of IMA and H-FABP usually had better sensitivity [96.3% (92.2-100%)] (P<0.05) and accuracy [92.6 (87.7-97.5%)] (P<0.05) than when individually used. Thus, the combination of H-FABP and IMA measurements after initiation of chest pain may be highly effective for risk stratification in patients with ACS and normal cardiac troponin T.

BACKGROUND

Novel preservation techniques may diminish ischemia/reperfusion (I/R) injury. Our preservation laboratory has modified Belzer MPS for machine perfusion (MP) with prostaglandin E1 (PGE 1), nitroglycerin (NTG), and polyethylene glycol-superoxide dismutase (PEG-SOD) to attenuate I/R injury. We reviewed our recent experience using this novel formulation (NF) compared with standard perfusates.

RESULTS

Between January 1998 and March 2000, 1060 consecutive kidneys were preserved in our laboratory. One hundred forty-eight kidneys (14%) were discarded. Fifty-eight percent of kidneys during this time period underwent MP (n = 532). En bloc kidney pairs were randomly assigned to pulsatile MP using Waters RM3 or MOX-100 perfusion systems using 1 of 3 perfusates; NF (NF; n = 119), Belzer MPS (MPS; n = 201), or Belzer II albumin gluconate (ALB; n = 212) Significant improvements in delayed graft function (DGF) rate were seen with NF versus other perfusates (8% vs 14% vs 19%, respectively; P =.03). At 6 months, graft survival was significantly improved with NF compared with MPS and ALB (96% vs 90% vs 87%, respectively; P =.03). NF also produced a significantly higher percentage of recipients with a serum creatinine level < or = 1.5 mg/dL.

CONCLUSIONS

Novel modifications of standard MP perfusate improved outcomes after renal transplantation. Preservation-based interventions targeted to ameliorate I/R injury can improve outcomes and may allow expansion of the donor pool.

OBJECTIVE

To investigate the effects of dexmedetomidine on oxidative injury caused by ionizing radiation.

METHODS

Randomized controlled experimental study.

METHODS

Department of radiation oncology and research laboratory of an academic hospital.

METHODS

Twenty-eight rats were randomized to 4 groups (n=7 per group). Group S rats were administered physiologic serum; group SR rats were administered physiologic serum and 10 Gy external ionizing radiation. Groups D100 and D200 were administered 100 and 200 μg/kg dexmedetomidine intraperitoneally, respectively, 45 minutes before ionizing radiation.

METHODS

Liver, kidney, lung, and thyroid tissue and serum levels of antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase, and catalase) and oxidative metabolites (advanced oxidation protein products, malondialdehyde, and nitrate/nitrite, and serum ischemia-modified albumin) were measured 6 hours postprocedure.

RESULTS

In group SR, IR decreased antioxidant enzyme levels and increased oxidative metabolite levels (P<.05). In plasma, antioxidant enzyme levels were higher and oxidative metabolite levels were lower in groups D100 and D200 than in group SR (P<.01). In tissues, hepatic and lung GPX levels were higher in groups D100 and D200 than in group SR (P<.001). Renal and thyroid GPX levels were higher in D200 than in group SR (P<.01). Thyroid superoxide dismutase levels were higher in groups D100 and D200 than in group SR (P<.01). Renal, lung, and thyroid catalase levels were higher in group D200 than in group SR (P<.01). Hepatic, renal, and lung advanced oxidation protein products and malondialdehyde levels were lower in groups D100 and D200 than in group SR (P<.01). Hepatic, renal, and lung nitrate/nitrite levels were lower in group D200 than in group SR (P<.05).

CONCLUSIONS

Dexmedetomidine preserves the antioxidant enzyme levels and reduces toxic oxidant metabolites. Therefore, it can provide protection from oxidative injury caused by ionizing radiation.

We report on the use of zeolites to limit the effects of reactive oxygen species (ROS) on human albumin under in vitro conditions. Zeolites of different structure type, channel size, channel polarity, and charge-compensating cation were screened for the elimination of ROS, notably HO(·), resulting from the Fenton reaction. A test based on ischemia-modified albumin (IMA) was used as a marker to monitor the activity of HO(·) after co-exposure of human serum to these zeolites. Two commercial zeolites, faujasite (FAU 13×, channel opening 0.74×0.74 nm with Na(+) as charge-compensating cation) and ferrierite (FER, channel opening 0.54×0.42 nm with H(+) as charge-compensating cation), were found to reduce IMA formation by more than 65% due to removal of HO(·) relative to reference values. It was established that partial ion exchange of the zeolites' respective charge-compensating cation vs. Fe(3+) implicated in the Fenton reaction plays a major role in HO(·) deactivation process. Moreover, our results show that no saturation of the respective zeolite active sites occurred. This is possible only when ROS are actively converted to water molecules within the zeolite void system, which generates H(+) ion transport. Because zeolites cannot be administered in blood, their use in medicine should be limited to extra corporeal circuits. Zeolites could be of use during cardiopulmonary bypass or hemodialysis procedures.

BACKGROUND

Deaths following diagnosis of venous thromboembolism (VTE) often result from another concurrent illness. The specificity of mortality markers predicting death from pulmonary embolism is unknown. The aim of this analysis was to compare blood predictors of death in patients with confirmed VTE to patients with negative investigations for VTE.

METHODS

Consecutive patients investigated for VTE were prospectively consented from a single hospital over 9months. VTE was diagnosed and excluded with a standard diagnostic algorithm. Blood was drawn for biomarker analysis and analyzed in batches for NT-proBNP, high sensitivity troponin T, C-reactive protein (CRP), fatty acid binding protein (FABP) and ischemia modified albumin (IMA). Participants were followed for 3months. The cohort was analyzed in two groups: those diagnosed with VTE and those who had thrombosis excluded. Regression analysis for 3-month mortality was performed for each group.

RESULTS

16/153 patients diagnosed with VTE died within three months (10.5%) as did 23/606 patients who had negative investigations for VTE (3.8%). Predictors for death following VTE included cancer, NT-proBNP, troponin T, FABP, and Hb<95g/L. NT-proBNP>500pg/ml in acute cancer associated VTE predicted death with C-statistic of 0.89 (0.80-0.99). Cancer, NT-proBNP and troponin T also predicted death in patients with negative investigations for VTE.

CONCLUSIONS

Several blood markers are not specific for death from PE and may be surrogate markers of global declining health.

BACKGROUND

The aims of this preliminary study were to determine the alteration of serum ischemia-modified albumin (IMA) levels and to investigate whether IMA may be used as an indicator of the cardioprotective efficacy of N-acetylcysteine (NAC) in patients undergoing coronary bypass grafting (CABG).

METHODS

Forty-four patients were randomized into one of two groups on the basis of cardioplegic strategies, either cold-blood cardioplegia enriched with NAC (50 mg/kg) or cold-blood cardioplegia alone. Serum IMA, cardiac troponin T (cTnT) and malondialdehyde (MDA) levels determined in NAC-enriched patients before and after CABG were compared with those of the NAC-free group. The albumin cobalt binding assay was used for IMA determination.

RESULTS

Serum IMA levels were significantly elevated after cross-clamping and peaked at 6 h after reperfusion in the two groups. In NAC-enriched patients, IMA levels determined 6, 12, 24 and 48 h after reperfusion were significantly lower than those of the NAC-free group (p < or = 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). IMA returned to baseline 24 h after reperfusion differently from cTnT and MDA in the NAC-enriched group.

CONCLUSIONS

IMA may be used as not only an indicator of myocardial ischemia-reperfusion injury, but also as a useful indicator of the cardioprotective effect of NAC in CABG.

The aim of this study was to assess the levels of oxidative, inflammatory, and fibrinolytic biomarkers as well as DNA strand breakage in hypercholesterolemic subjects. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, total protein, albumin, apolipoprotein (Apo) A, Apo B, advanced oxidation protein products (AOPP), increased ischemia-modified albumin (IMA), -SH, NOx, IL-6, and D-dimer levels were assessed, and DNA strand breakage was evaluated using comet assay in 38 patients with hypercholesterolemia and 20 healthy controls. Total cholesterol, triglycerides, LDL cholesterol, Apo A, Apo B, AOPP, IMA, IL-6, and D-dimer concentrations were significantly higher in subjects with hypercholesterolemia. However, NOx and plasma -SH group concentrations were lower in hypercholesterolemic subjects, while no significant differences were observed with respect to DNA strand breakage between the two groups. Hypercholesterolemia is related to oxidative stress and inflammation. Accordingly, AOPP concentration was higher in subjects with hypercholesterolemia, and we speculate that AOPP can reflect the enhancement of protein oxidation and inflammation.

Cardiovascular disease (CVD) is the leading cause of fatality and disability worldwide regardless of gender. Obesity has reached epidemic proportions in population across different regions. According to epidemiological studies, CVD risk markers in childhood obesity are one of the significant risk factors for adulthood CVD, but have received disproportionally little attention. This review has examined the evidence for the presence of traditional cardiac biomarkers (nonspecific; lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, myoglobulin, glycogen phosphorylase isoenzyme BB, myosin light chains, ST2, and ischemia-modified albumin) and novel emerging cardiac-specific biomarkers (cardiac troponins, natriuretic peptides, heart-type fatty acid-binding protein, and miRNAs). Besides, noninvasive anatomical and electrophysiological markers (carotid intima-media thickness, coronary artery calcification, and heart rate variability) in CVDs and obesity are also discussed. Modifiable and nonmodifiable risk factors associated with metabolic syndrome in the progression of CVD, such as obesity, diabetes, hypertension, dyslipidemia, oxidative stress, inflammation, and adipocytokines are also outlined. These underlying prognostic risk factors predict the onset of future microvascular and macrovascular complications. The understanding of invasive and noninvasive cardiac-specific biomarkers and the risk factors may yield valuable insights into the pathophysiology and prevention of CVD in a high-risk obese population at an early stage.

Ischemia-modified albumin (IMA) is considered to be a novel biochemical marker for ischemic and atherosclerotic conditions. This study aimed to investigate the influence of ezetimibe monotherapy on circulating IMA levels in hypercholesterolemic patients. A total of 31 patients (mean age 65.7 years) received 10 mg of ezetimibe daily during a 12-week treatment period. The levels of low-density lipoprotein cholesterol and IMA were significantly reduced after ezetimibe treatment. The adjusted regression analyses revealed that the changes in the IMA levels were not significantly correlated with those of the other atherosclerotic risk markers, such as body mass index, blood pressure, glucose and lipid panels. The significant reduction of the IMA levels following ezetimibe treatment, which was independent of the reduction of low-density lipoprotein cholesterol levels, suggests that ezetimibe may improve the oxidative stress burden in hypercholesterolemic patients.

BACKGROUND

Ischemia-modified albumin is an altered serum albumin that forms under conditions of oxidative stress, a state also associated with doxorubicin-induced myocardial injury.

OBJECTIVE

The aim of this study was to better assess diagnostic and prognostic significance of ischemia-modified albumin in patients with breast cancer undergoing doxorubicin chemotherapy.

METHODS

Blood samples were collected from 152 breast cancer patients before and after each cycle of doxorubicin chemotherapy to measure the serum levels of ischemia-modified albumin, cardiac troponin T and creatine kinase-MB. We also monitored cardiac function during a 12 month follow-up.

RESULTS

There was a significant difference in ischemia-modified albumin levels before and after each cycle of chemotherapy and the ischemia-modified albumin concentration positively correlated with the cumulative dose of doxorubicin (r = 0.212, P < 0.05). The combination of ischemia-modified albumin with cardiac troponin T and creatine kinase-MB increased the sensitivity to 0.920 and the specificity to 0.830 in the diagnosis of doxorubicin-induced myocardial injury. The optimal cutoff for ischemia-modified albumin concentration was 112.09 U/ml. The rate of change for ischemia-modified albumin levels correlated negatively with the rate of change for left ventricular ejection fraction at one year (r = -0.221, P < 0.05).

CONCLUSIONS

Ischemia-modified albumin may be a clinically potential new marker for diagnosing doxorubicin-induced myocardial injury, and is helpful to predict long-term impairment of cardiac function.

BACKGROUND

A hypoxic intrauterine environment is believed to play a pivotal role in physiological trophoblast development. Ischaemia-modified albumin (IMA) is used in the measurement of cardiac ischaemia. We aimed to test the hypothesis that maternal serum IMA may be elevated in early pregnancy as a measurable manifestation of intrauterine ischaemia.

METHODS

Prospective observational study in healthy women with singleton pregnancies (n=66) and non-pregnant controls (n=26). Maternal serum IMA levels were measured at 11-13 weeks of gestation and in non-pregnant women.

RESULTS

The median IMA level in the pregnant group [115.14 kU/l; interquartile range (IQR) 102.33-124.71 kU/l] was significantly higher (P<0.001) than in non-pregnant controls (73.71 kU/l; IQR 60.38-82.78 kU/l). During pregnancy, absolute values of IMA were higher than the concentration used for the diagnosis of myocardial ischaemia (>95 kU/l) in 86% of women.

CONCLUSIONS

In early pregnancy, IMA levels were above the concentration used for the diagnosis of myocardial ischaemia in most women, and should therefore not be used as a marker for cardiac ischaemia in pregnancy. Maternal serum IMA is elevated to supra-physiological levels in early normal pregnancy supporting the hypothesis that normal trophoblast development is associated with a hypoxic intrauterine environment, although other mechanisms leading to an IMA increase cannot be excluded.

This study was conducted to investigate whether albumin-adjusted ischemia-modified albumin index (IMA index) is more sensitive and accurate than ischemia-modified albumin (IMA) as early detection marker of ischemic stroke, and to compare IMA and IMA index in progression and non-progression of ischemic stroke. This case-control study was done at an emergency medical center of a university hospital. 52 patients with neurological symptoms were enrolled (28 Ischemic Stroke Group and 24 Non-Stroke Group). In the ROC analysis of IMA index to diagnose stroke, area under the curve (AUC) was 0.990 (cutoff value 91.4; 95% CI: 0.970-1.000; sensitivity: 96.4%; specificity 95.8%). The AUC for IMA value was 0.928 (cutoff value 98 U/ml; 95% CI 0.857-0.999; sensitivity 89.3%; specificity 88.5%). [corrected] The difference between progression (n = 12) and non-progression group (n = 16) in IMA and IMA index were statistically insignificant (p>> 0.01). IMA index was more sensitive than conventional IMA value as diagnostic biomarker of stroke, however, arguable as a predictive biomarker for progression of ischemic stroke.

OBJECTIVE

This study aimed at evaluation of ischemia-modified albumin (IMA), malondialdehyde (MDA), and advanced oxidative protein products (AOPP) as markers of vascular injury in diabetic nephropathy (DN) with derivation of cutoff values for the same.

METHODS

Study population comprised 60 diabetes patients and 30 controls, with diabetes patients further categorized into three groups based on urine albumin/creatinine ratio (UACR) of <30 mg/g (diabetes without microalbuminuria), 30-300 mg/g (early DN), and >300 mg/g of creatinine (overt DN). Serum IMA, MDA, and AOPP were estimated by enzyme-linked immunosorbent assay; HbA1c, serum creatinine, urine albumin, and urine creatinine were estimated using automated analyzers. Statistical analysis was done using analysis of variance, Pearson's correlation coefficient, and receiver-operating characteristic curve.

RESULTS

A statistically significant difference was found in the levels of IMA among patients with early DN (154 ng/mL), diabetes without nephropathy (109.4 ng/mL), and healthy controls (45.7 ng/mL), with highest levels in early DN cases. Similar increase was seen in AOPP as well. A significant correlation was observed between IMA and UACR in diabetes without nephropathy (r = 0.448).

CONCLUSIONS

The present study postulates serum IMA as a novel biomarker for the assessment of disease progression in diabetes even before microalbuminuria, and a cutoff point ≥99 ng/mL can be used for detection of early DN.

OBJECTIVE

In normal pregnancies, a hypoxic intrauterine environment seems necessary for early trophoblast development. In this context, maternal serum levels of ischemia-modified albumin (IMA) are elevated, reflecting the oxidative stress associated with placental development. The aim of this study was to evaluate IMA and pregnancy-associated plasma protein A (PAPP-A) in mothers bearing small-for-gestational-age (SGA) fetuses compared to normal pregnancies.

METHODS

A prospective study was performed between June 2010 and June 2011. Serum total albumin, IMA and PAPP-A concentrations were determined in 81 pregnant women in three different periods: 1st trimester, 2nd trimester and postpartum. Two groups of subjects were retrospectively identified: Group (1) mothers bearing appropriate-for-gestational-age (AGA) fetuses, and Group (2) mothers bearing SGA fetuses. Serum total albumin and IMA concentrations were determined in 198 non-pregnant women as controls.

RESULTS

Serum IMA concentrations increase during gestation. IMA/albumin serum levels in the 1st trimester were significantly higher in subjects of Group (2) (p<0.05), whereas values of serum PAPP-A MoM were significantly lower (p<0.05).

CONCLUSIONS

Elevated IMA serum levels together with low levels of PAPP-A were detected in the 1st trimester in mothers bearing SGA fetuses, and this may reflect early placental changes occurring before clinical manifestation of SGA.

Ischemia-modified protein (IMA) is the most sensitive diagnostic biomarker of ischemic heart disease, but differentiation of IMA from human serum albumin (HSA), a ubiquitous serum protein, is still challenging owing to the shared antigenicity. In this investigation, we developed a rapid and interference-free approach for IMA determination using quantum dots-coupled X-ray Fluorescence Spectroscopy (Q-XRF). In a typical Q-XRF assay, serum total HSA is quantified using quantum dot-coupled sandwich immunoassay, and intact HSA (iHSA) is determined using a XRF spectroscopy, by measuring XRF intensity of Co (II) bonded to iHSA. IMA concentration is automatically determined within 30 min by calculating the difference between total HSA and iHSA. This strategy can effectively eliminate the interference from native HSA level. Results show that no significant influences have been observed from hemolysis or high levels of cholesterol (7 mg/L), triglyceride (5.2 mg/L), IgG (10 g/L), and fibrinogen (4 g/L). A linearity of 1-100mg/mL is obtained in iHSA determination using XRF (r(2)=0.979). The proposed Q-XRF assay demonstrates a lowest detection limit of 0.05 U/mL. Receiver-operating characteristic (ROC) curves reveal that Q-XRF assay provide an improved sensitivity than ACB assay (95.9% vs. 82.9%) in differentiating ischemic patients from health individuals, at an optimal cutoff point of 79.2U/mL. The proposed approach provides a new strategy for interference-free, simple and rapid evaluation of IMA concentration by combining sandwich immunoassay and XRF spectroscopy.