Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease. We aimed to measure the level of miR-155 and its genetic variant rs767649 in patients with RA and to evaluate their relationship with ischemia-modified albumin (IMA). The study was performed on 79 patients with RA (group I) and 78 healthy control participants (group II). Quantitative real-time polymerase chain reaction was used to assess the expression of serum miR-155 in addition to its functional variant rs767649. IMA levels were measured by enzyme-linked immunosorbent assay. Significant overexpression of miR-155 and higher levels of IMA were detected in patients with RA compared with those in controls (P < 0.0001). The fold change in miR-155 was significantly positively associated with IMA (r = 0.362, P = 0.001) in patients with RA. Significant differences in the frequency of miR-155 (rs767649) genotypes and alleles were noted between patients with RA and controls. MiR-155 and IMA levels were significantly associated with the genotype distribution of miR-155 (rs767649) in patients with RA and were higher in patients with the TT genotype. MiR-155 and its functional variant rs767649 might play an important role in susceptibility to the increased risk of RA, stressing the role of miR-155 as a therapeutic target in the treatment of RA. In addition, IMA levels were increased and correlated with miR-155 and its single nucleotide polymorphism rs767649 in Egyptian patients with RA.

Background: Molecular imaging with molecularly targeted probes is a powerful tool for studying the spatio-temporal interactions between complex biological processes. The pivotal role of the receptor for advanced glycation end products (RAGE), and its involvement in numerous pathological processes, aroused the demand for RAGE-targeted imaging in various diseases. In the present study, we evaluated the use of a diagnostic imaging agent for RAGE quantification in an animal model of peripheral artery disease, a multimodal dual-labeled probe targeted at RAGE (MMIA-CML).

Methods: PAMAM dendrimer was conjugated with Nε-carboxymethyl-lysine (CML) modified albumin to synthesize the RAGE-targeted probe. A control untargeted agent carried native non-modified human albumin (HSA). Bifunctional p-SCN-Bn-NOTA was used to conjugate the ⁶⁴Cu radioisotope. Surgical right femoral artery ligation was performed on C57BL/6 male mice. One week after femoral artery ligation, mice were injected with MMIA-CML or MMIA-HSA labeled with ⁶⁴Cu radioisotope and 60 min later in vivo microPET-CT imaging was performed. Immediately after PET imaging studies, the murine hindlimb muscle tissues were excised and prepared for gene and protein expression analysis. RAGE gene and protein expression was assessed using real-time qPCR and Western blot technique respectively. To visualize RAGE expression in excised tissues, microscopic fluorescence imaging was performed using RAGE-specific antibodies and RAGE-targeted and -control MMIA.

Results: Animals subjected to PET imaging exhibited greater MMIA-CML uptake in ischemic hindlimbs than non-ischemic hindlimbs. We observed a high correlation between fluorescent signal detection and radioactivity measurement. Significant RAGE gene and protein overexpression were observed in ischemic hindlimbs compared to non-ischemic hindlimbs at one week after surgical ligation. Fluorescence microscopic staining revealed significantly increased uptake of RAGE-targeted nanoparticles in both ischemic and non-ischemic muscle tissues compared to the control probe but at a higher level in ischemic hindlimbs. Ischemic tissue exhibited explicit RAGE dyeing following anti-RAGE antibody and high colocalization with the MMIA-CML targeted at RAGE.

Conclusions: The present results indicate increased expression of RAGE in the ischemic hindlimb and enable the use of multimodal nanoparticles in both in vitro and in vivo experimental models, creating the possibility for imaging structural and functional changes with a RAGE-targeted tracer.

Keywords: AGEs; Ischemia; Molecular imaging; RAGE.

OBJECTIVE

To investigate the diagnostic value of ischemia-modified albumin (IMA) in the diagnosis oflpatients with aortic aneurysm.

METHODS

The study group consisted of 98 patients who presented to our university hospital emergency department with aortic pathology and were definitively diagnosed using spiral tomography. The control group consisted of 101 healthy individuals with similar demographic characteristics.

RESULTS

Mean IMA values were 0.89 +/- 0.21 absorbance units (ABSU) in the aortic aneurysm group (P < 0.001), 0.70 +/- 0.12 ABSU in the aortic dissection group (P < 0.001), 0.98 +/- 0.23 ABSU in the aneurysm and dissection group (P < 0.001), 0.84 + 0.16 ABSU in the aneurysm and rupture group (P < 0.001), and 0.87 +/- 0.27 ABSU in the aneurysm, dissection, and rupture group (P < 0.001). Mean IMA value for the subjects in the control group was 0.62 +/- 0.17 ABSU. All the differences between the aortic pathology groups' IMA values and those of the control group were statistically significant (P < 0.001).

CONCLUSIONS

On the basis of the findings from this study, serum IMA levels are higher in patients with aortic pathology compared to healthy individuals. This finding suggests that IMA may help to diagnose aortic pathology, but it requires confirmation by additional clinical studies.

BACKGROUND

Ischemia modified albumin (IMA) has emerged as a marker for ischemic injury and oxidative damage, particularly in myocardial infarction. There are very few studies on the significance of IMA in other conditions associated with ischemia. The complications of diabetes mellitus (DM) arising out of poor glycaemic control have an underlying ischemic aetiology.

OBJECTIVE

To evaluate correlation of IMA with glycaemic control in type 2 DM (T2DM). Secondary aim was to assess the utility of IMA as a marker for vascular complications in T2DM.

METHODS

During this cross-sectional study, a total of 100 diagnosed cases of T2DM were recruited between May 2013 and September 2013. The IMA, HbA1c, lipid profile, creatinine and urine micro-albumin levels were measured and analysed with respect to clinical condition of the patients.

METHODS

The epidemiological software, Epi-Info 7.1.5, was used for the statistical analysis, p-value<0.05 was defined as level of significance.

RESULTS

The study subjects were in the age group from 30 to 75 years and 52.4% were males. There was a great degree of variance in the level of glycaemic control and majority (64.6%) had poor or very poor glycaemic control as reflected by their HbA1c levels. The IMA (Mean ± SEM) levels were found to be higher (62.9 ± 1.7ABSU) in the patients with poor glycaemic control compared to those with good glycaemic control (54.2 ± 3.5 ABSU, p-value < 0.05) and correlated with HbA1c levels (r(2)=0.14). IMA levels also appeared to be related with the changes in lipid profile and increased with increasing total cholesterol levels. The subjects with macro-vascular complications (retinopathy and neuropathy) showed non-significantly higher levels of IMA. The elevation in IMA correlated with the HbA1c and changes in the lipid profile.

CONCLUSIONS

IMA correlates with poor glycaemic control and dyslipidaemia associated with T2 DM and could serve as an indicator of oxidant stress in these patients.

The objective of this study was to assess the albumin cobalt binding (ACB) test in a cohort of type 2 diabetes patients. The ACB test is a simple, inexpensive, sensitive and robust test that could have important clinical application in detecting complications of type 2 diabetes mellitus.

We tested patients with type 2 diabetes without any clinically detectable complications or without any other comorbid conditions for serum ACB levels along with an equal number of age- and sex-matched healthy control subjects. ACB levels were compared after the patients with diabetes were investigated for various complications using standard statistical tests of significance.

A total of 100 patients with type 2 diabetes were studied with age- and sex-matched healthy control subjects. Of the 100 patients, 78 had different complications on detailed laboratory testing. The patients with complications had significantly higher ACB test results when compared to the patients with diabetes without complications and to that of the control subjects (0.62 ± 0.04, 0.42 ± 0.07, 0.30 ± 0.05absorbance units (ABSU)/mL, respectively. P < 0.001). All values in diabetics were significantly higher than that of controls.

The serum ACB test is a sensitive indicator of complications developed in type 2 diabetes mellitus. Patients may be followed up with ACB results to detect early complications in this disease.

OBJECTIVE

Ischemia-modified albumin (IMA) has been widely accepted as a serological biomarker. IMA has been proposed as a simple and novel marker of oxidative stress in preeclampsia (PE). This systematic review and diagnostic test accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel serological biomarker, IMA to detect PE.

METHODS

A systematic search of major databases was performed to identify all published diagnostic accuracy studies on IMA. Risk of bias and applicability concerns were assessed for included studies. Summary estimates; the pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects models. The overall test performance was summarized using summary receiver operating characteristic (SROC) curve analysis.

RESULTS

Six articles were included in this meta-analysis. The overall estimates of IMA in detecting PE were pooled sensitivity; 0.80 (95%CI 0.73-0.86), pooled specificity; 0.76 (95%CI 0.70-0.81), DOR; 14.32 (95%CI 5.06-40.57), and area under curve (AUC); 0.860. There was no between-study heterogeneity due to threshold effect.

CONCLUSIONS

This meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy (AUC = 0.860). However, further research is needed for re-evaluation and clinical validation of fairly promising results of this meta-analysis.

Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction.

Oxidative stress (OS) has been reported to be associated with the pathogenesis of polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) levels in the circulation have been recently studied as a novel marker of OS. The studies in the literature on IMA levels in PCOS are inconsistent. This meta-analysis was conducted to compare circulatory IMA levels between PCOS patients and non-PCOS controls. Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The funnel plot analysis with Begg's and Egger's tests was used for publication bias. A total of nine studies were included in this meta-analysis. The results indicated that the serum IMA levels were significantly elevated in PCOS patients as compared to non-PCOS controls (SMD = 0.49, 95% CI = 0.23-0.75, Z = 3.75, p = .0002). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the good validity and stability of these meta-analytic results. There was no evidence of publication bias as evidenced by the Egger (p = .28) and Begg's tests (p = .21). The present meta-analysis suggests that IMA might be considered as a reliable and novel marker reflecting increased OS in PCOS.

Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin. Albumin binds most metal ions and harbours four primary metal binding sites: site A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous efforts to clarify the identity of IMA and the causes for its reduced cobalt-binding capacity were focused on the NTS site, but the degree of N-terminal modification could not be correlated to the presence of ischemia. More recent work suggested that Co2+ ions as used in the ACB assay bind preferentially to site B, then to site A, and finally to the NTS. This insight paved the way for a new consistent molecular basis of the ACB assay: albumin is also the main plasma carrier for free fatty acids (FFAs), and binding of a fatty acid to the high-affinity site FA2 results in conformational changes in albumin which prevent metal binding at site A and partially at site B. Thus, this review advances the hypothesis that high IMA levels in myocardial ischemia and many other conditions originate from high plasma FFA levels hampering the binding of Co2+ to sites A and/or B. This is supported by biophysical studies and the co-association of a range of pathological conditions with positive ACB assays and high plasma FFA levels.

BACKGROUND

Biomarkers of myocardial necrosis may be increased in patients with chronic heart failure. We investigated whether ischaemia-modified albumin (IMA), a marker of ischaemia, is also elevated in patients with compensated heart failure, due to dilated cardiomyopathy (DCM).

METHODS

We studied 42 patients with DCM and an equal number of age-matched normal volunteers. We assessed IMA serum levels with the albumin cobalt binding test.

RESULTS

IMA was 89.9 +/- 13.1 (71-117) KU/L in the patient group and 93.9 +/- 9.9 (76-122) KU/L in the control group, with no significant difference between the two (P = 0.11). However, IMA differed significantly according to the New York Heart Association classification (P = 0.003) and was negatively correlated with the left ventricular ejection fraction (r = -0.40, P = 0.014).

CONCLUSIONS

We conclude that IMA, a marker of ischaemia, does not differ in patients with clinically stable DCM compared with normal subjects, but varies significantly in relation to the severity of the disease.

BACKGROUND

Myocardial ischemia may alter the metal binding capacity of circulating serum albumin. Thus, the aim of this study was to describe an automated method to measure ischemia-induced alterations in the binding capacity of serum albumin for exogenous nickel, and to evaluate the diagnostic characteristics of this assay for the assessment of acute coronary syndrome (ACS) in patients presenting to the emergency room (ER) with acute chest pain.

METHODS

We assessed the concentrations of cardiac troponin I (cTnI), serum albumin, ischemia-modified albumin (IMA) measured by the cobalt-albumin binding assay (CABA), and by an automated nickel-albumin binding assay (NABA) in the following groups: ACS (n=63) and non-ischemic chest pain (NICP, n=26). Biochemical markers were determined in blood samples obtained from patients within 3 h of ER admission.

RESULTS

cTnI, CABA and NABA concentrations were higher in ACS group in comparison to the NICP group. A significant correlation between NABA and CABA was observed (r=0.5387, p<0.001). Areas under the curve for CABA and NABA were 0.7289 and 0.7582, respectively. Both CABA and NABA have the ability to discriminate patients with ACS. However, NABA has a slightly higher ability to discriminate ACS compared with CABA.

CONCLUSIONS

Patients with ACS have reduced nickel binding to human serum albumin, and NABA may have an important role as an early marker of myocardial ischemia, particularly in patients presenting to the ER with acute chest pain.

BACKGROUND

Oxidative stress has important role in the pathophysiology of diabetic retinopathy (DR). Ischemia modified albumin (IMA) has been recently considered as a marker of oxidative damage in diabetes. However, there is scarcity of published information about both IMA and albumin adjusted-IMA (AAIMA) in DR patients.

OBJECTIVE

To evaluate the serum levels of IMA and AAIMA in patients with DR and in healthy controls.

METHODS

This was a cross sectional study. Serum was obtained to measure lipids, albumin and IMA from the the patients with DR and non-diabetic subjects. The IMA level was measured by a colorimetric albumin cobalt binding (ACB) assay and the values were presented as absorbance units (ABSU). The IMA levels were adjusted for albumin interference and the AAIMA by using a formula [Individual serum albumin/median albumin concentration of the population X IMA].

RESULTS

This study was done on 18 DR and 20 non- diabetic patients. The mean Serum IMA values in DR group and controls were 0.50±0.17 and 0.32±0.17, respectively (P=0.002). The mean serum AAIMA values in DR group and controls were 0.48±0.20 and 0.32±0.17, respectively (P=0.01). The albumin and HDL- Cholesterol levels were significantly lower in DR patients compared to controls (p=0.004 and p=0.01, respectively).

CONCLUSIONS

The level of IMA and AAIMA were higher in cases of DR compared to that of non-diabetic subjects. The levels of albumin and HDL-Cholesterol were lower in DR patients compared to controls.

BACKGROUND

The diagnosis of acute coronary syndrome remains challenging, as cardiac troponins and creatine kinase-MB do not detect myocardial ischemia. Ischemia modified albumin is biomarker positive within 6-10 minutes following ischemic onset, where oxygen free radicals leads to reduction in binding capacity of human serum albumin to transitional metal-cobalt. The objective of this study was to compare ischemia modified albumin between acute coronary syndrome patients and healthy controls, and evaluate diagnostic performance of ischemia modified albumin compared to cardiac troponins, creatine kinase-MB and electrocardiogram in acute coronary syndrome patients.

METHODS

Fifty ACS patients and 50 healthy controls were enrolled in this cross-sectional study. Ischemia modified albumin was measured after addition of known amount of cobalt to human serum albumin, followed by spectrophotometric determination of unbound cobalt fraction at 470 nm using dithiothreitol as coloring agent. Independent student t-test and One-way ANOVA to compare differences of mean between groups; diagnostic sensitivity and specificity of ischemia modified albumin was determined by receiver operating characteristic curve; McNemar-test was used to assess diagnostic performance of entire test parameters, when used alone and in combinations.

RESULTS

Ischemia modified albumin was significantly higher in acute coronary syndrome patients compared to controls (0.823±0.191 vs 0.410±0.081)(p<0.001). Receiver operating characteristic curve derived optimal cut-off of 0.475 Absorbance unit had sensitivity and specificity of 92% and 82% respectively (area under curve- 0.96). However, no significant differences in mean ischemia modified albumin values between three categories of acute coronary syndrome were seen. Sensitivity of ischemia modified albumin assay (92%) was significantly higher compared to electrocardiogram (72%), cardiac troponin I (18%), and creatine kinase-MB(42%).

CONCLUSIONS

Ischemia modified albumin is elevated in acute coronary syndrome patients with better diagnostic performance compared to electrocardiogram, cardiac troponin I, and creatine kinase-MB for early diagnosis, however, with limited ability to discriminate between ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina.

Protein oxidation has been demonstrated in preeclampsia, but this finding has not been established in other hypertensive disorders in pregnancy (HDP). The present study comparatively evaluated ischemia modified albumin (IMA) and advanced oxidation protein products (AOPP) in different HDP and investigated their association with total antioxidant activity (AOA) and total thiols. There was a significant increase in AOPP and IMA, a significant decrease in AOA, total thiols and albumin in every HDP compared to controls. Among HDP groups, eclampsia patients showed more significant change in each of the parameter. IMA and AOPP were negatively associated with AOA in every HDP and with total thiols only in eclampsia. The present study supports the hypothesis of oxidative stress, as evidenced by increased protein oxidation, decreased antioxidant status and significant negative association between protein oxidation and AOA in every HDP. The imbalance of prooxidants and antioxidants was further augmented in eclampsia.

Background: Birth asphyxia is a leading cause of neonatal mortality. Ischemia-modified albumin (IMA) levels may have a predictive role in the identification and prevention of hypoxic disorders, as they increase in cases of ischemia of the liver, heart, brain, bowel, and kidney.

Purpose: This study aimed to assess the value of IMA levels as a diagnostic marker for neonatal hypoxic-ischemic encephalopathy (HIE).

Methods: Sixty newborns who fulfilled 3 or more of the clinical and biochemical criteria and developed HIE as defined by Levene staging were included in our study as the asphyxia group. Neonates with congenital malformation, systemic infection, intrauterine growth retardation, low-birth weight, cardiac or hemolytic disease, family history of neurological diseases, congenital or perinatal infections, preeclampsia, diabetes, and renal diseases were excluded from the study. Sixty healthy neonates matched for gestational age and with no maternal history of illness, established respiration at birth, and an Apgar score ≥7 at 1 and 5 minutes were included as the control group. IMA was determined by double-antibody enzymelinked immunosorbent assay of a cord blood sample collected within 30 minutes after birth.

Results: Cord blood IMA levels were higher in asphyxiated newborns than in controls (250.83±36.07 pmol/mL vs. 120.24±38.9 pmol/mL). Comparison of IMA levels by HIE stage revealed a highly significant difference among them (207.3±26.65, 259.28±11.68, 294.99±4.41 pmol/mL for mild, moderate, and severe, respectively). At a cutoff of 197.6 pmol/mL, the sensitivity was 84.5%, specificity was 86%, positive predictive value was 82.8%, negative predictive value was 88.3%, and area under the curve was 0.963 (P<0.001).

Conclusion: IMA levels can be a reliable marker for the early diagnosis of neonatal HIE and can be a predictor of injury severity.

Keywords: Hypoxic-ischemic encephalopathy; Ischemia modified albumin.

Aim This study aims to evaluate hypoxia/ischemia and oxidant stress, and negative neurodevelopmental outcomes in small-for-gestational-age (SGA) infants. Material and Methods Two study groups were established as SGA and appropriate-for-gestational-age (AGA) infants. SGA infants were allocated asymmetric and symmetric SGA infants. Serum levels of neuron-specific enolase (NSE), ischemia-modified albumin (IMA), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were determined and oxidative stress indexes (OSI) were calculated in all groups. Results Overall, 83 infants were diagnosed SGA, and 85 infants were determined AGA. TOS and OSI levels were significantly higher and TAC levels were significantly lower in SGA group (p < 0.05). MDA and IMA levels were significantly higher in SGA group (p < 0.05). NSE levels in SGA infants were significantly higher (p < 0.05). NSE and IMA were significantly higher in symmetric SGA infants (p < 0.05). TOS, OSI, MDA, TAC levels were not significantly different in SGA infants with abnormal neurological findings (p>> 0.05); NSE and IMA levels were significantly higher in SGA group with abnormal neurological findings (p < 0.05). Conclusion SGA infants expose to hypoxia and oxidative stress led to neuronal damage. We suggest that in addition to NSE, IMA blood levels might be a sensitive novel marker for predicting the severity of neuronal damage.

This study aims to evaluate differences in myocardial toxicity induced by different chemotherapy regimens. Patients were divided into 2 groups: epirubicin (EPI) combined with cyclophosphamide (EC) group and docetaxel combined with cyclophosphamide (TC) group. Changes in electrocardiograph (ECG) and ischemia-modified albumin (IMA) were determined pre- and 1, 3, and 6 courses of postchemotherapy. After the first course of chemotherapy, there was no significant difference in ECG and abnormal IMA incidence rates between the TC groups and EC groups (P>> .05). After the third course and at the end of the sixth course, ECG and abnormal IMA incidence rates in the EC group were significantly higher than in the TC group (P < .05). Besides, IMA values significantly increased with the increase in chemotherapy courses in the EC group; and the value of the postsixth course was significantly higher than in the pre- and postfirst and -third courses of chemotherapy. IMA value in the postsixth course in the TC group was significantly higher than that in the pre- and postfirst and -third courses of chemotherapy. In addition, IMA values at the postfirst and -third courses of chemotherapy in the EC group were significantly higher than in the TC group. Both EC and TC chemotherapy regimens were harmful to the myocardium, and the incidence rate of myocardial damage increased with the increase of cumulative dose. Besides, the degree of myocardial damage in EC group was significantly higher than in the TC group.

OBJECTIVE

This study aimed to determine the association between early pregnancy loss and serum ischemia-modified albumin (IMA) concentrations.

METHODS

Serum samples of 180 women that included healthy pregnant women, women admitted for termination of pregnancy due to the absence of fetal cardiac activity or absence of fetal pole on ultrasonographic examination, and healthy non-pregnant women attending for gynecological examination. Each group included 60 patients. Serum concentrations of IMA were compared among the groups, and the correlations with patients' age, gravidity, BMI, gestational age and total serum albumin concentrations were calculated.

RESULTS

When the groups were compared with respect to IMA concentrations, the group with early pregnancy loss was found to have significantly higher IMA concentrations (p < 0.001). An IMA threshold of >163 ng/mL had a sensitivity of 75%, specificity of 55% to discriminate between healthy pregnant patients and patients with early pregnancy loss in first trimester.

CONCLUSIONS

Our findings support the theory that possible oxidative stress, a more hypoxic environment and defective placentation lead to increased serum IMA concentrations. These findings may help to shed light on the complicated pathogenesis of early pregnancy loss.

Objective. To investigate serum levels of free β-HCG, progesterone, and ischemia-modified albumin (IMA) and their combined use in the prediction of first trimester abortions. Methods. A total of 156 pregnant women between 5 and 13 weeks of gestational age were included in this study. At admission, serum levels of free β-HCG, progesterone, and IMA were noted and all cases were divided into two groups; Group I (n = 77) resulted in abortion including missed abortion, incomplete/complete abortion, and inevitable abortion whereas Group II (n = 79) included normal pregnancies. Results. Compared to Group II, the significantly decreased value of free β-HCG progesterone and significantly increased value of IMA were found in Group I (P < 0.01, P < 0.01, P < 0.01, resp.). When combining all three parameters, sensitivity 75%, specificity 99%, PPV 98%, and NPV 76% were obtained. The multivariate logistic regression analysis revealed the free β-HCG, progesterone, and IMA independent factors in the prediction of abortions. Conclusions. The combined use of free β-HCG, progesterone, and IMA levels can be useful in the prediction of first trimester spontaneous abortions.

Background: This study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS).

Methods: 80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined.

Results: The average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to below. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality.

Conclusions: We can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.

Uvod: Plan ove studije je bio da istraži vezu dinamične tiol/disulfidne homeostaze i prognoze mijelodisplastičnog sindroma (MDS).

Metode: U istraživanje je uključeno 80 pacijenata kojima je dijagnostifikovan MDS između 2012. i 2017, starijih od 18 godina, i 80 zdravih kontrolnih ispitanika. MDS dijagnoza je potvrđena imunološkim bojenjem koštane srži dobijene aspiracionom biopsijom. Ispitani su dinamična tiol/disulfidna homeostaza i nivoi albumina modifikovanog ishemijom (IMA).

Rezultati: Otkriveno je da su vrednosti prosečnog IMA (0,71 ± 0,08 nasuprot 0,67 ± 0,09; p = 0,002), vrednost medijane disulfida (18,0 naspram 11,6; p < 0,001) i disulfid/nativniog tiola (6 naspram 3; p < 0,001) i medijane disulfid/ukupnog tiola (5,4 naspram 2,9; p < 0,001) veće kod bolesnika sa MDS-om u poređenju sa kontrolnom grupom. Takođe, otkrivene su i niske vrednosti medijane hemoglobina, belih krvnih zrnaca, neutrofila, limfocita, prosečnog nativnog tiola (290,7 ± 48,5 naspram 371,5 ± 103,8; p < 0,001), prosečnog ukupnog tiola (328,2 ± 48,9 u odnosu na 393 ± 105,5; p <0,001) i prosečnog nativnog tiola/ukupni tiol (%) (88,3 ± 4,3 prema 94,2 ± 2,1; p < 0,001). Faktori rizika poput bolesti kolagenskih tkiva (HR: 9,17; p = 0,005), MDS-EB-1 (HR: 10,14; p = 0,032), MDS-EB-2 (HR: 18,2; p = 0,043), i disulfid/nativni tiol (HR: 1,17; p = 0,023) su otkriveni kao nezavisni prediktori koji predviđaju napredovanje do akutne mijeloidne leukemije. Po Koksovom modelu regresije, faktori rizika kao što su starost (HR: 1,05; p = 0,002), MDS-EB-1 (HR: 12,58; p <0,001), MDS-EB-2 (HR: 5,75; p = 0,033), disulfid/nativni tiol (HR: 1,14; p = 0,040) i hemoglobin (HR: 0,64; p = 0,007) smatraju se prediktorima smrtnosti.

Zaključak: Možemo tvrditi da bi dinamička tiol-disulfidna homeostaza mogla da ima značajne efekte i na etiopatogenezu i na preživljavanje pacijenata sa MDS-om i da bi mogla biti uključena u nove prognostičke skoring sisteme.

Keywords: disulfide; mercaptan; myelodysplasia; oxidative stress; thiol.

Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.

The aim of the study was to analyze the clinical value of the combined detection of ischemia-modified albumin (IMA), D-dimer (D-D) and monocyte chemoattractant protein-1 (MCP-1) in the diagnosis of acute myocardial infarction (AMI). Altogether 87 patients with AMI from January 2017 to January 2018 were enrolled in the AMI group, and 82 patients without coronary artery disease were included in the control group. The serum levels of IMA, D-D, MCP-1, cardiac troponin (CTnT) and high-sensitivity C-reactive protein (hs-CRP) in the two groups were detected by ELISA. The blood lipids of the two groups and the levels of IMA, D-D, MCP-1 after treatment were detected. The association between IMA, D-D, MCP-1, CTnT, hs-CRP and blood lipid in patients with AMI was analyzed. The values of IMA, D-D, and MCP-1 alone and combined in the diagnosis of AMI were analyzed by ROC curve. The levels of IMA, D-D, MCP-1, CTnT and hs-CRP in the AMI group were significantly higher than those in the control group (P<0.05). The levels of IMA, D-D and MCP-1 in the patients with poor prognosis were significantly higher than those of the good prognosis group (P<0.05). The changes of IMA, D-D and MCP-1 levels were positively correlated with the levels of CTT and hs-CRP (P<0.05). The AUC, specificity and sensitivity of patients with AMI diagnosed with MCP-1 alone were 0.8084, 81.61 and 69.51%, respectively. Those of patients diagnosed by D-D were 0.7302, 59.77 and 81.71%, those of patients diagnosed by IMA alone were 0.7289, 58.62 and 80.49%, and those of patients detected by the combination of MCP-1, D-D and IMA were 0.9047, 58.62 and 93.90%. In conclusion, the levels of IMA, D-D and MCP-1 in AMI patients are higher than those in the control group. The levels of IMA, D-D and MCP-1 were positively correlated with CTnT and hs-CRP levels in AMI patients. Combined detection of IMA, D-D, and MCP-1 can improve the accuracy.

Keywords: AMI; D-D; IMA; MCP-1; clinical prognosis; combined detection.