Ischemia-Modified albumin (IMA) has been used as an early marker in the evaluation of the patients with acute coronary syndrome. We aimed to evaluate IMA in end-stage renal disease (ESRD) patients on hemodialysis and the effect of albumin methods on albumin-adjusted IMA levels. A total of 30 ESRD patients were included in this study. Serum IMA and albumin levels were measured before and after a hemodialysis session. Albumin concentrations were determined with bromocresol green and bromocresol purple methods. Postdialysis IMA and albumin-adjusted IMA levels with two different albumin methods were significantly increased compared with the predialysis levels (P<0.05). However, we did not find any difference in albumin-adjusted IMA levels in either at the beginning or at the end of the dialysis session. IMA levels increase after hemodialysis, whereas albumin method has no effect on albumin-adjusted IMA levels.

The biomarker "ischemia-modified albumin" (IMA), measured by the albumin-cobalt-binding assay (ACB assay), is the only FDA-approved biomarker for early diagnosis of myocardial ischemia. On the basis of the hypothesis that high levels of free fatty acids are directly responsible for reduction in cobalt binding by albumin, chemically defined model systems consisting of bovine serum albumin, Co(2+), and myristate were studied by isothermal titration calorimetry, (111)Cd NMR spectroscopy, and ACB assays. Significantly reduced Co(2+) binding to albumin, as demonstrated by an increase in the absorption of the Co-dithiothreitol adduct, elicited by adding ca. 3 mol equiv of myristate, was comparable to that observed in clinical ACB assays. Levels of free fatty acids are elevated during myocardial ischemia but also in other conditions that have been correlated with high IMA values. Hence, IMA may correspond to albumin with increased levels of bound fatty acids, and all clinical observations can be rationalized by this molecular mechanism.

Ischemia-modified albumin (IMA) levels have been advocated as a biomarker for evaluating the oxidative stress status. No data are showed on the potential role of IMA in type 1 diabetes (T1D). We aimed to establish the correlation among serum levels of IMA, C-reactive protein (CRP), and diabetic ketoacidosis (DKA) in patients with T1D. Fifty-seven patients with T1D, 27 patients with DKA, and 40 controls were enrolled. Serum IMA and CRP levels were measured and evaluated to distinguish from DKA. CRP and IMA levels were significantly elevated in patients with DKA at admission to the hospital compared to non-DKA and control subjects. CRP and IMA levels were higher in non-DKA patients than in controls. CRP, plasma glucose, and IMA levels were reduced after insulin treatment. Serum IMA levels were an independent risk marker for DKA (OR = 1.225, p = 0.002, 95 % CI: 1.076-1.394). Receiver operating characteristic curve analyses showed no difference in the areas under curve for serum IMA and CRP values. This study indicates that IMA and CRP levels were significantly correlated with DKA diagnosis. IMA can act as a biomarker that reflects the presence of DKA.

BACKGROUND

Impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases like cancer. The aim of this study was to evaluate the levels of the novel marker ischemia modified albumin (IMA) and albumin adjusted-IMA (Adj-IMA) in patients with bladder cancer (BC) as well as its association with total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI).

METHODS

Forty male patients with BC (mean age, 67.4±12 years) and forty age-sex matched healthy persons (mean age 56.0±1.7 years) were included in this study. Serum levels of IMA, TAS, TOS were analyzed and Adj- IMA and OSI was calculated.

RESULTS

Serum IMA, TOS and OSI values were significantly higher in patients with BC compared to controls (p<0.0001, p=0.01 and p=0.01, respectively), whereas TAS was significantly lower in BC patients (p=0.04). There was no significant difference for serum albumin-adjusted IMA levels between groups (p=0.4).

CONCLUSIONS

In this study, it was found that there was an impaired oxidative/antioxidant status in favor of oxidative stress in BC patients. This observation was not confirmed by Adj-IMA calculation. There is no published report about serum concentrations of IMA in patients with BC. Further studies are needed to establish the relationship of IMA and oxidative stress parameters in BC and the significance of IMA to other cancers.

Ischemia modified albumin (IMA) and Protein Carbonyl (PC) have known as proteins that are modified on the similar basis of oxidative stress induced protein modification and may have diagnostic potential in acute myocardial infarction. This study aims to evaluate the ability of using IMA and PC content to diagnose Non-ST elevation myocardial infarction (NSTEMI) and efficiency of combining these two markers. Serum from NSTEMI and healthy control were determined for serum IMA and PC content. The results showed that both of serum IMA level and PC content in NSTEMI was significantly higher than that of healthy controls. However, the PC content showed greater diagnostic performance than IMA. Combinatorial determination of serum IMA level with PC content level was enhanced test efficiency. In conclusion, our finding demonstrated that IMA and PC content can be used as a diagnostic marker for NSTEMI.

BACKGROUND

It has been proposed that reactive oxygen species (ROS) generated during myocardial ischemia-reperfusion modify the N-terminus of serum albumin resulting in ischemia-modified albumin (IMA) formation. Likewise, several recent publications provide evidence that melatonin, a circadian endogenously produced indolamine, is a direct scavenger of ROS. We sought to investigate the relationship between IMA and melatonin in ST- elevation myocardial infarction (STEMI).

METHODS

We compared IMA and melatonin levels in 27 patients with STEMI undergoing primary angioplasty and 20 age- and gender-matched healthy normal subjects. Blood samples were drawn at 02:00h (night period) and 09:00h (day period) while patients were resting, to assess IMA and melatonin.

RESULTS

In both groups, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less in the STEMI-patients than in the control group (p<0.001). In contrast to findings about melatonin, IMA levels showed no diurnal variations in control subjects. However, the STEMI group showed a diurnal fluctuation with significantly higher levels at 02:00h (p<0.01). The association between IMA and melatonin remained statistically significant after adjustment for cardiovascular risk factors. An inverse correlation between IMA and melatonin at 02:00h and at 09:00h was observed, with respective r-values of -0.42 (p<0.03) and -0.57 (p<0.002).

CONCLUSIONS

Circulating IMA is negatively correlated to melatonin in STEMI-patients. Our results suggest that melatonin might exert a beneficial effect as a radical scavenger in a human model of myocardial ischemia-reperfusion.

BACKGROUND

Reduction of Sheng-Nao-Kang decoction (RSNK), composed of Salvia miltiorrhiza Bge., Ligusticum chuanxiong Hort., Astragalus membranaceus (Fisch.) Bunge., Pueraria lobata (Willd.) Ohwi., Paeonia lactiflora Pall. and Panax notoginseng (Burk.) F. H. Chen., is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which has been investigated its protective effect on focal cerebral ischemia-reperfusion injury in rat in our previous report.

OBJECTIVE

To evaluate the antithrombotic effect of RSNK in blood stasis model rats and explore the potential mechanisms.

METHODS

Subcutaneous injection of norepinephrine and bovine serum albumin combined with ice water bath was used to establish the acute blood stasis rat model. The anticoagulant activities were investigated by measuring activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and the content of fibrinogen (FIB). Meanwhile, the levels of thromboxane A2 (TXA2), prostaglandins I2 (PGI2), endothelial nitric oxide synthase (eNOS) and endothelin (ET) were detected.

RESULTS

The treatment of RSNK was able to prolong APTT, TT and PT, and decrease FIB content obviously. Furthermore, it markedly suppressed TXB2 level and up-regulated 6-keto-PGF1α level of the blood-stasis model rats, accompanied with the decrease of T/K. The level of ET and TXA2 in plasma was down-regulated and the levels of eNOS in plasma and PGI2 in serum was up-regulated in RSNK-treated rats compared with model rats (P<0.05).

CONCLUSIONS

The present study suggested that RSNK possessed remarkable antithrombotic property in blood stasis model rats induced by ice water bath and subcutaneous injection of norepinephrine and bovine serum albumin. This property could be associated with its anticoagulation activity, the regulation of active substances in vascular endothelium and maintaining the balance of TXA2 and PGI2.

We investigated the relationship of ischemia-modified albumin (IMA) and high-sensitivity C-reactive protein (hsCRP) levels with direct (endocan) and indirect (carotid intima-media thickness [cIMT] and 24 hours urine protein excretion) endothelial dysfunction indicators in type 2 diabetes mellitus (T2DM). Patients with T2DM (n = 88) and 88 healthy individuals were included in the study. The median endocan (475.15 vs 216.37 pg/mL; P < .001, respectively) and hsCRP (10.74 vs 3.11 mg/L; P < .001, respectively) and the mean IMA (0.64 ± 0.12 vs 0.51 ± 0.12 absorbance units; P < .001, respectively) levels were higher in participants with endothelial dysfunction compared to those without endothelial dysfunction in T2DM. The 24-hour urine protein excretion and cIMT levels had a positive correlation with hsCRP ( r = .357; P = .001 and r = .592; P < .001, respectively), IMA ( r = .519; P < .001 and r = .495; P < .001, respectively) and endocan ( r = .347; P = .001 and r = .583; P < .001, respectively) levels in the T2DM group. Stepwise multivariable logistic regression analysis, which included laboratory findings found to be associated with endothelial dysfunction, showed that endocan (odds ratio [OR] = 1.456; P = .004), hsCRP (OR = 1.298; P = .008), and IMA (OR = 2.270, P = .003) were independent risk factors. It was found that none of these markers were superior in terms of diagnostic discrimination for endothelial dysfunction. Endocan, IMA, and hsCRP levels were found to be associated with endothelial dysfunction in patients with T2DM.

OBJECTIVE

We examined serum ischaemia-modified albumin (IMA) levels in normal pregnant and preeclamptic women. The primary aim of our study was to assess IMA in women with mild and severe preeclampsia.

METHODS

Serum ischaemia-modified albumin levels were measured in 18 normotensive and 36 preeclamptic pregnant women by enzyme linked immuno-sorbent assay. Patients were subdivided as having either mild (n=18) or severe preeclampsia (n=18). Receiver operating characteristic curve was constructed, and sensitivity and specificity were calculated based on the best cut-off.

RESULTS

IMA levels were significantly higher in the mild and severe preeclamptic groups than in the control group. IMA with a cut-off point of 0.31 identified women with preeclampsia with sensitivity 80% and specificity 77.8%.

CONCLUSIONS

Our study demonstrates that serum levels of IMA correlate with severity of preeclampsia.

OBJECTIVE

To investigate the diagnostic accuracy of presentation ischaemia-modified albumin (IMA), in addition to cardiac troponin I (TnI), as a strategy to rapidly ascribe low risk to patients with chest pain attending an emergency department, and to determine whether IMA has the potential to reduce transit time in emergency departments.

METHODS

A prospective observational study was carried out in two emergency departments (belonging to the John Radcliffe Hospital, Oxford, UK; and the Frenchay Hospital, Bristol, UK) of similar size. Consecutive adult patients presenting with features of possible ischaemic cardiac chest pain and a normal electrocardiogram were eligible. The index test (measurement of IMA and TnI at presentation) and reference standard (delayed TnI measurement, taken at least 8 h after pain onset) were applied to all recruited patients. All clinicians were blinded to the results of the index test. Assays were carried out in a single laboratory using standard techniques.

RESULTS

399 patients were recruited; 277 patients had a result for both the index test and reference standard. The sensitivity was 97.6% (95% confidence interval (CI) 87.4 to 99.9), negative predictive value 97% (95% CI 84.2 to 99.9) and specificity 13.6% (95% CI 9.5 to 18.7). Sensitivity analysis showed similar findings in three alternative scenarios. Receiver operating characteristic analysis indicated that a different "cut-off" value for IMA would not improve the properties of the test. The median potential time saved (n = 268) was 6 h and 10 min.

CONCLUSIONS

The diagnostic accuracy of presentation IMA in this study does not support its use as an effective risk stratification tool for patients with chest pain in the emergency department. The sensitivity is insufficiently high, with a small number of false negatives undermining the safety of the test. Frequent false positives produce a low specificity that limits the practical value of the test.

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. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis 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 problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin(R), has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting 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 in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS.

Cardioprotection is an all-encompassing term for physico-biochemical or therapeutic interventions which slow or ameliorate the progression of cardiomyocyte necrosis. There are a number of established and novel biomarkers to assess coronary artery disease at initiation, ischemia, necrosis and myocardial dysfunction. Established biomarkers such as creatine kinase-MB, cardiac troponins and natriuretic peptides have been utilized for the assessment of cardioprotection, especially during surgery. Novel markers are currently being investigated for detection and risk assessment in patients with acute coronary syndromes. Ischemia-modified albumin is used for the early detection of cardiac ischemia and could be a potential biomarker for assessing the early cardioprotective effects of damage-limiting interventional measures.

Medical ozone has therapeutic properties as an antimicrobial, anti-inflammatory, modulator of antioxidant defense system. Major ozonated autohemotherapy (MOA) is a new therapeutic approach that is widely used in the treatment of many diseases. The objective of the present study was to determine whether preischemic application of MOA would attenuate renal ischemia-reperfusion injury (IRI) in rabbits. Twenty-four male New Zealand white rabbits were divided into four groups, each including six animals: (1) Sham-operated group, (2) Ozone group (the MOA group without IRI), (3) IR group (60 min ischemia followed by 24 h reperfusion), and (4) IR + MOA group (MOA group). The effects of MOA were examined by use of hematologic and biochemical parameters consisting of neutrophil to lymphocyte ratio (NLR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, the histopathological changes including the tubular brush border loss (TBBL), tubular cast (TC), tubular necrosis (TN), intertubular hemorrhage and congestion (IHC), dilatation of bowman space (DBS), and interstitial inflammatory cells infiltration (IECI) were evaluated. In the IR group, compared to the Sham group, biochemical parameters indicating oxidative stress, NLR, IL-6, TNF-α, IMA, TOS, and OSI have increased. MOA reduced inflammation and oxidative stress parameters. Although TAS values have decreased in the IR group and increased in the MOA-pretreated group, no significant changes in TAS values were detected between the IR and MOA groups. The total score was obtained by summing all the scores from morphological kidney damage markers. The total score has increased with IR damage when compared with the Sham group (13.83 ± 4.30 vs 1.51 ± 1.71; p = 0.002). But, the total score has decreased significantly after application of MOA (5.01 ± 1.49; p = 0.002; compared with the IR group). MOA preconditioning is effective in reducing tissue damage induced in kidney ischemia-reperfusion injury. The protective effect of MOA is mediated via reducing inflammatory response and regulating of reactive oxygen species (ROS). Renal histology also showed convincing evidence regarding MOA's protective nature against kidney injury induced renal ischemia-reperfusion. Consequently, MOA might be helpful in protecting the kidneys from IR-induced damage in humans, probably through the anti-inflammatory effect and reducing the total oxidant status.

High homocysteine (Hcy) levels are a well-known independent risk factor for endothelial damage in atherosclerosis. We examined whether a rat intestinal model of ischemia-reperfusion was associated with high Hcy and with the modification of plasma albumin into cysteinylated species (CysAlb). The three treatment groups were as follows: midline abdominal incision (group A, n=10), followed by ligation of the superior mesenteric artery for a period of 2h (group B, n=3), and followed by reperfusion for 1h (group C, n=10). Hcy levels were 2.5-fold higher in group C than group A (p<0.05). 100% and 73.44+/-0.04% of Alb were modified into Cys species in groups C and B, respectively, compared to 51.2% in group A. A cystathionine beta-synthase (CBS) deficient mouse model, known to have high plasma Hcy levels, was also used to determine the extent of CysAlb. Hcy levels, %CysAlb, and %HcyAlb were 180.1+/-45.7 microM, 0%, and 23.4+/-4.4% in CBS deficient mice, while in control mice, those values were 5.7+/-1.8 microM, 24.2+/-4.1%, and 0%, respectively (p<0.05). High CysAlb and Hcy levels were observed in a rat model of bowel ischemia/reperfusion while high HcyAlb and Hcy levels with no CysAlb were observed in the CBS deficient mice. CysAlb may serve as a biomarker for the severity of gut ischemia, and high Hcy may explain endothelial damage associated with this model. Additionally, active CBS is essential for the formation of CysAlb.

The early diagnosis of myocardial ischaemia is problematic in patients with ESRD (end-stage renal disease). The aim of the present study was to determine whether IMA (ischaemia-modified albumin) increases during dobutamine stress and detects myocardial ischaemia in patients with ESRD. A total of 114 renal transplant candidates were studied prospectively, and all received DSE (dobutamine stress echocardiography). IMA levels were taken at baseline and 1 h after cessation of DSE. A total of 35 patients (31%) had a positive DSE result. Baseline IMA levels were not significantly different in the DSE-positive and -negative groups. The increase in IMA was significantly higher in the DSE-positive group compared with those with no ischaemic response (26.5 +/- 19.1 compared with 8.2 +/- 9.6 kU/l respectively; P = 0.007; where kU is kilo-units). From ROC (receiver operator charactertistic) curve analysis, the optimal IMA increase to predict an ischaemic response was 20 kU/l, with a sensitivity of 81% and a specificity of 72% [area under the curve, 0.80 (95% confidence interval, 0.44-0.94); P = 0.03]. There were 18 deaths, ten of which were cardiac in nature over a follow up period of 2.25 +/- 0.71 years. An increase in IMA>> or = 20 kU/l was associated with significantly worse survival (P = 0.02). In conclusion, IMA is a moderately accurate marker of myocardial ischaemia in ESRD. Patients with an increase in IMA>> or = 20 kU/l during DSE had significantly worse survival.

Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed.

BACKGROUND

Ischaemia-modified albumin (IMA) is a new sensitive diagnostic biochemical marker of myocardial ischaemia. The purpose of the study was to analyse the prognostic value of IMA in patients admitted for non-ST-segment elevation acute coronary syndromes (NSTE ACS).

METHODS

Consecutive patients admitted for NSTE ACS in our institution were prospectively included. IMA, cardiac troponin I (TnI) and C-reactive protein (CRP) were measured in all patients within 3h of last chest pain. The clinical combined endpoint was major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction (MI) and recurrent ischaemia leading to urgent revascularization. The independent prognostic impact of IMA on occurrence of the combined endpoint during hospitalization and at 1 year was tested by a logistic regression model and was systematically adjusted for other known clinical and biological predictors.

RESULTS

Seventy-nine patients were enrolled. Nine (11.4%) patients experienced the combined endpoint during hospitalization and 16 (20.2%) during 1-year follow-up. Median IMA level was significantly higher in patients with MACE during hospitalization (115 [93-126]U/mL versus 100 [42-138]U/mL; p=0.007) and at 1 year (114 [93-126]U/mL versus 97 [42-138]U/mL; p<0.001). After adjustment for conventional prognostic risk factors, IMA remained an independent predictor of MACE both during hospitalization (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.01-1.16; p=0.03) and at 1 year (hazards ratio [HR]: 1.07; 95% CI: 1.03-1.12; p=0.003).

CONCLUSIONS

Baseline levels of IMA were associated with both short- and long-term cardiovascular (CV) events in patients admitted for NSTE ACS.

OBJECTIVE

Chronic heart failure (CHF) is accompanied by increased adenosine plasma levels (APLs). It is unknown whether adenosine release occurs at the peripheral level or whether the myocardium itself is the source of adenosine release. To answer this question, we evaluated APLs in the coronary sinus of CHF patients during a resynchronisation procedure and compared the values with those at the peripheral level. We also investigated a possible correlation between APLs and ischaemia-modified albumin (IMA) levels, a useful marker of tissue ischaemia.

METHODS

19 men and seven women were prospectively included. Blood samples for APLs were collected simultaneously from a brachial vein (peripheral) and from the coronary sinus. Blood samples for brain natriutretic peptide (BNP) and IMA were collected from a brachial vein.

RESULTS

APLs from the brachial vein were higher than those from the coronary sinus (1.69 vs 0.75 muM p<0.01). IMA levels were correlated with APLs from the brachial vein (r = 0.59, p<0.01). BNP concentrations were correlated with APLs from the brachial vein (r = 0.73, p<0.001) but not with APLs from the coronary sinus (r = 0.38, p>0.05). BNP concentrations and IMA levels were correlated (r = 0.71, p<0.001).

CONCLUSIONS

In CHF patients, adenosine release occurs at a peripheral level and not at the myocardium level.

OBJECTIVE

Fast intravenous (i.v.) iron administration during hemodialysis (HD) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers, which are also induced by the hemodialysis procedure itself. The aim of this study was to investigate if slow i.v. iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session.

METHODS

Twenty dialysis patients 30-92 years of age that were iron replete and had values for hemoglobin, transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions. In the first session patients did not receive any iron treatment, whereas during the second and the third session patients received slow (60 min) i.v. infusions of 100 mg of iron sucrose and 100 mg of iron dextran, respectively. Blood samples were drawn before the hemodialysis session, 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions, for the measurement of markers of oxidant stress (oxidized LDL and ischemia-modified albumin) and inflammation (high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-alpha).

RESULTS

Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied. In contrast, ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration. High-sensitivity CRP, IL-6 and TNF-alpha were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern.

CONCLUSIONS

We did not find an increase in the markers of oxidation/inflammation studied, after slow i.v. iron administration during hemodialysis session.

OBJECTIVE

We investigate the efficacy of serial ischemia-modified albumin (IMA) measurements in diagnosis and follow-up of necrotizing enterocolitis (NEC), and compare its effectiveness with C-reactive protein (CRP), interleukin-6 (IL-6), in NEC.

METHODS

Preterm infants, whose gestational age and weight matched each other, were grouped as control (n = 36) and NEC (n = 37). IMA, CRP, IL-6 levels were measured on the third day of life for the control group and on the day of diagnosis (first day), third, and seventh days of NEC.

RESULTS

IMA, CRP, and IL-6 levels were significantly increased in NEC patients compared to the control group (P < 0.001) on the follow-up. IMA levels were significantly higher in infants with stage-III NEC than those in infants with stage-II NEC on the first, third, and seventh days (P < 0.001). The area under curve for IMA (0.815 at diagnosis, 0.933 at the third day, 0.935 at the seventh day) were significantly higher than CRP and IL-6 at all days for predicting perforation in infants with NEC (P < 0.001). Similarly, the area under curve for IMA (0.952 at diagnosis, 0.929 at the third day, 0.971 at the seventh day) was significantly higher than CRP and IL-6 at all consequent days of diagnosis for predicting mortality in infants with NEC (P < 0.001).

CONCLUSIONS

Ischemia-modified albumin was found to be superior to CRP and IL-6 in both diagnosis and follow-up of NEC.

BACKGROUND

Ischemia-modified albumin (IMA) is an emerging marker of ischemia. To investigate the applicability of IMA for the diagnosis of skeletal muscle ischemia, we examined IMA changes as measured by the albumin-cobalt binding test, in a group of healthy volunteers after standardized exercise-induced calf muscle ischemia.

METHODS

A total of 12 healthy volunteers underwent standardized exercise on a plantar flexion pedal. Ischemic conditions were achieved by inflating a femoral blood pressure cuff at incremental pressures of 0, 60, 90, 120 and 150 mm Hg. Calf muscle ischemia was identified by synchronous 31P magnetic resonance spectroscopy, measuring intracellular concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi). In addition, IMA, serum albumin, lactate, troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and at 5, 10, 30, 360 and 720 min after cuff release.

RESULTS

Magnetic resonance spectroscopy showed calf muscle ischemia in all participants upon exercise and cuff inflation. Circulating IMA concentrations increased significantly after cuff release (p=0.03) and returned to baseline within 30 min. While we found a significant negative correlation with albumin, there was no association of IMA levels with lactate or intracellular levels of PCr or Pi in samples obtained at baseline and post-ischemia. TnT and NT-proBNP remained within the normal range throughout the observation period in all participants.

CONCLUSIONS

IMA may represent a clinical marker for skeletal muscle ischemia, although its lack of specificity requires careful clinical interpretation of data. The short period of IMA elevation after ischemic exercise requires standardized conditions for use as a diagnostic tool and hints at IMA applicability as a marker of prolonged or chronic ischemia.

BACKGROUND

Ischemia-modified albumin (IMA), a protein elevated in cardiac ischemia, is also increased to supra-physiological levels in early normal pregnancy. This finding supports the hypothesis that normal trophoblast development is stimulated by a hypoxic intrauterine environment. The aim of this study was to examine whether first trimester IMA levels are further elevated with defective trophoblast development.

METHODS

Prospective study of healthy women with singleton pregnancies undergoing nuchal translucency assessment at 11-14 weeks. First trimester maternal serum IMA concentrations in those subsequently developing pre-term pre-eclampsia (n = 19) were compared to randomly chosen controls with normal pregnancy outcome (n = 69).

RESULTS

Median first trimester serum IMA concentrations were significantly higher in women who subsequently developed pre-eclampsia (median 126.5 kU/L, interquartile range (IQR) 114.33-134.36 kU/L) when compared to those with normal pregnancy outcome (median 115.01 kU/L, IQR 102.29-124.81 kU/L, P = 0.02).

CONCLUSIONS

Maternal serum IMA levels are elevated in the first trimester in women with pre-eclampsia, a clinical manifestation of defective endovascular trophoblast development. This suggests that abnormally high intrauterine hypoxia and subsequent reperfusion oxidative damage may be associated with defective trophoblast development. First trimester serum IMA may be a potential biomarker for abnormal placental development.

OBJECTIVE

Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury.

METHODS

Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically.

RESULTS

All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions.

CONCLUSIONS

Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.

OBJECTIVE

To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients.

METHODS

Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated.

RESULTS

The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters.

CONCLUSIONS

The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis.