Background/aim: To evaluate the potential protective effects of Boric Acid (BA) in experimental cholestatic liver ischemia reperfusion (IR) injury model.

Materials and methods: The study included 24 female rats which were divided into 3 groups each containing 8 rats. The control group (Group 1) only received laparotomy. In the IR group (Group 2) biliary tract ligation was applied and 1 week later 45 minutes ischemia and 1 hour reperfusion with relaparotomy without any treatment was implemented. In the treatment BA+IR group (Group 3). 1 week after the biliary ligation intraperitoneal administration of 200 mg/kg BA was given 10 minutes before the ischemia for 45 minutes and reperfusion for 1 hour with relaparotomy. Liver tissue and blood samples were taken for histopathological and biochemical examination. Ischemia modified albumin (IMA), SCUBE1, total antioxidant status (TAS) and total oxidant status (TOS) levels were also examined.

Results: Compared to control, groups IR and BA+IR had higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total and direct bilirubin levels. Albumin value was high in the control group and low in the other groups. In terms of IMA levels there was no significant difference between groups (p>0.05). When SCUBE-1 levels were examined groups IR and BA+IR were significantly higher than the group 1. TAS was highest in the group BA+IR whereas TOS was highest in the group IR and lower in the group BA+IR. In histopathological analysis, loss of intercellular border loss in hepatocytes, diffuse nuclear pycnosis and mild to moderate neutrophilic cell infiltration were observed in the IR group. Statisticaly significant dissociation, hemorrhage and severe neutrophilic cell infiltration were seen in hepatocytes of rats with IR (p<0.05).

Conclusion: BA has promising results in the treatment of experimental IR injury of the cholestatic liver because of its antioxidant effects. It may be used in clinical practice after more extensive studies about the effects of BA on IR injury of the cholestatic liver.

Keywords: Boric acid; cholestasis; ischemia reperfusion; liver.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are considered a new class antidiabetic agent, As well as lowering blood sugar, it has many positive effects. This study aims to investigate the effects of SLGT2i on the gastric mucosa.

Materials and methods: We investigated the effects of empagliflozin on indomethacin-induced gastritis using 48 male Wistar Albino rats. We performed histopathological evaluations of gastric mucosa tissue. And, we studied the levels of serum disulfide, native thiol, total thiol, and ischemia modified albumin (IMA), disulfide/native thiol ratio (SSSH), native thiol/total thiol percent ratio (SH total SH), and disulfide/total thiol percent ratio (SS total SH).

Results: We found that empagliflozin increased mucin production in rat gastric mucosa. Besides, we observed milder inflammation findings and lower gastritis scores in the empagliflozin receiving groups than the placebo groups. Native thiol, total thiol, and disulfide levels were lower in the indomethacin-induced gastritis groups.

Conclusions: This study is the first study to investigate the effect of empagliflozin on the gastrointestinal tract in a rat model. We concluded that empagliflozin increased mucin production and revealed positive effects in an indomethacin-induced gastritis model.

Background: We aimed to evaluate the value of ischemia modified albumin (IMA) as a prognostic marker in acute pancreatitis (AP) patients, determine whether it is efficient in assessing the disease severity or not, and to estimate the correlation between IMA and the inflammatory markers, prognostic markers and scoring systems routinely used in clinical practice.

Methods: 100 adult patients (18 years and older) who have been hospitalized and evaluated with AP diagnosis in Tepecik Training and Research Hospital,, Department of Gastroenterology, between April 1, 2017 and April 1, 2018 have been enrolled in the study. Patients have been stratified disease etiology (biliary or non-biliary). The non-biliary group has been divided into subgroups as alcoholic, lipemic, or idiopathic. Disease severity has been categorized as mild, moderate, or severe pancreatitis according to the Atlanta classification. Ranson, Harmless Acute Pancreatitis Score (HAPS), Bedside Severity Index for Acute Pancreatitis (BISAP) scores have been determined for each patient. Patients have been grouped as necrotizing or edematous according to the Atlanta classification.

Results: According to our findings, IMA has been found to be correlated with disease severity, Ranson and BISAP scores, and procalcitonin levels. We have observed that some laboratory parameters including blood urea nitrogen and hematocrit levels and HAPS scoring system are not correlated to IMA.

Conclusion: Our study is the first study to compare multiple prognostic factors with IMA in AP patients. In our study, the association between IMA and AP has been evaluated in the context of prognostic scoring and disease severity.

Introduction: The SARS-CoV-2 virus affects many organs, especially the lungs, with widespread inflammation. We aimed to compare the endogenous oxidative damage markers of coenzyme Q10, nicotinamide dinucleotide oxidase-4, malondialdehyde, and ischemia-modified albumin levels in patients with pneumonia caused by SARS-CoV-2 and in an healthy control group. We also aimed to compare these parameters between patients with severe and non-severe pulmonary involvement.

Methods: The study included 58 adult patients with SARS-CoV-2 pneumonia and 30 healthy volunteers. CoQ10 and MDA levels were determined by high-pressure liquid chromatography. NOX4 and IMA levels were determined by ELISA assay and colorimetric method.

Results: Higher levels of CoQ10, MDA, NOX4, and IMA and lower levels of COQ10H were observed in patients with SARS-CoV-2 pneumonia than in the control group. MDA, IMA, NOX4, and CoQ10 levels were significantly higher in patients with severe pulmonary involvement than in patients with non-severe pulmonary involvement, but no significant difference was observed in CoQ10H levels. CoQ10 levels were significantly and positively correlated with both ferritin and CRP levels.

Conclusion: SARS-CoV-2 pneumonia is significantly associated with increased endogenous oxidative damage. Oxidative damage seems to be associated with pulmonary involvement severity.

Keywords: COVID-19; CoQ10, NOX4; Oxidative damage; Pneumonia.

This study was undertaken due to the urgent need to explore reliable biomarkers for early SARS-CoV-2 infection. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers IL-6, TNF-α, N-terminal pro-B natriuretic peptide, cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and pregnancy-associated plasma protein-A (PAPP-A) in 84 patients with COVID-19.Patients were divided into three groups according to their RT-qPCR and IgG values: acute infection (n = 35), early infection (n = 25) or control subjects (n = 24). Levels of biomarkers were analyzed in patient serum samples using commercially available ELISA kits. Results showed a significant increase in IMA and PAPP-A levels in the early infected patients. Moreover, multivariate analysis and receiver operating characteristic (ROC) curve showed that IMA and PAPP-A had excellent discrimination value for the early stage of COVID-19. For IMA, the area under the ROC curve (AUC) had a value of 0.94 (95% confidence interval (CI): 0.881-0.999). Likewise, the serum level of PAPP-A was significantly higher in patients with early infection than in the control subjects (AUC = 0.801 (95% CI: 0.673-0.929)). The combined use of IMA and PAPP-A enhanced the sensitivity for total SARS-CoV-2-infected patients to 93%. These results suggest that the increased levels of PAPP-A and IMA shed light on underlying mechanisms of COVID-19 physiopathology and might be used as efficient biomarkers with high sensitivity and specificity for the early stage of COVID-19. Importantly, when monitoring pregnancy and cardiovascular diseases using PAPP-A or IMA levels, a SARS-CoV-2 infection should be discarded for proper interpretation of the results.

Keywords: COVID-19; SARS-CoV-2; biomarkers; coronavirus; ischemia-modified albumin; pregnancy-associated plasma protein-A.

Circulating microRNAs (miRNAs) have been reported dysregulated during exercise. However, the changes of specific serum miRNAs during the 5-km run test with intensity of 51-52% maximum oxygen uptake (V̇O₂max) and their association with traditional cardiovascular-related indicators remain well-characterized. Levels of miR-1, miR-21, miR-146a, miR-155, miR-181, and miR-210 were detected in 120 young subjects before and after the exercise training by quantitative reverse-transcription PCR (RT-qPCR). Besides, the levels of cardiac troponin I (cTNI), myoglobin (Myo), creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), ischemia-modified albumin (IMA), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured and the correlation between levels of serum miRNAs and biochemical parameters was also analyzed. Compared with resting state, the serum levels of miR-1, miR-146a, miR-155, miR-181, and miR-210 were significantly increased after exercise training. Serum levels of miR-146a, miR-155, and miR-210 after exercise training were positively correlated with Myo, CK-MB, and LDH, respectively, while miR-1, miR-146a, miR-181, and miR-155 were positively correlated with the levels of IL-6. Additionally, all the five miRNAs were negatively correlated with IMA levels. The multivariate logistic regression analysis showed that high levels of miR-146a, AST, LDH, and IL-6 in serum were risk factors, while low IMA contents were a protective factor for cardiovascular adaptation during exercise. In conclusion, the dynamic changes of miRNAs under the condition of the 5-km continuous running contribute to the adaptive regulation of the cardiovascular function of the body.

Keywords: 5-km run test; adaptation; cardiovascular disease; exercise; microRNAs.

Background: The trio Essential Thrombocytosis (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PM) are BCR-ABL negative myeloproliferative neoplasms. All three diseases have the risk of transforming into acute leukemia. Oxidative stress and some genetic mutations increase the risk of leukemic transformation. The median age in patients with ET, PV, and MF is around 64 years, and it is expected to exceed 65 in the coming years. Since oxidative stress increases with age, we aimed to evaluate the oxidative stress parameters in older patients with myeloproliferative neoplasms.

Methods: The study included a total of 160 patients (57 patients with Essential Thrombocytosis, 52 patients with Primary Myelofibrosis, and 51 patients with Polycythemia Vera) and 56 healthy controls, aged 65 and over. Ischemia Modified Albumin (IMA) and thiol parameters (native thiol, total thiol, and disulfide) were studied from serum samples taken at the time of diagnosis.

Results: The median age of the patients was 69 (65 - 85) years. Patients had higher levels of IMA and lower levels of thiol compared to the control group (p < 0.001). When evaluated according to disease subgroups, it was observed that the highest IMA levels and the lowest thiol levels were in patients with PM (p < 0.001). Higher IMA levels and lower native thiol levels were found in patients with the ASXL1 mutation (p < 0.001).

Conclusions: Serum IMA and thiol levels are also significantly changed in older patients with BCR-ABL negative myeloproliferative neoplasia. Changes in these markers are independent of age. Disease-associated mutations such as ASXL1 can also affect the serum levels of these markers.

The aim of the present study was to assess thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with Wilson Disease (WD) and to compare them to healthy controls. Methods: Based on the inclusion and exclusion criteria, fifteen children with WD and twenty-nine healthy children were enrolled, and serum thiol/disulfide and IMA levels were compared between groups. Results: The mean values of native and total thiols were significantly lower in the WD group than in the control group. The mean value of disulfide was significantly higher in the WD group than in the control group. The mean percentages of disulfide/total thiol and native thiol/total thiol were higher in the WD group than in the control group. The IMA value was also higher in the WD group than in the control group. Conclusion: The present study demonstrating altered thiol/disulfide parameters indicates increased oxidative stress in children with WD.

Keywords: Disulfide; Wilson disease; thiol.

Introduction: Ischaemia-modified albumin (IMA) is a new, sensitive marker of ischaemic diseases that has been approved for diagnosing myocardial ischaemia. However, the accuracy of IMA in the diagnosis of stroke remains to be clarified. The study's purpose is to assess the potential role of IMA as a diagnostic indicator in stroke.

Methods: We carried out a systematic search in Medline, the Cochrane Library, Embase, Scopus, Science Direct, ISI Web of Knowledge, and the reference lists of relevant articles from the databases' inception to September 1, 2019. Studies that appraised the diagnostic accuracy of IMA for acute stroke patients were included in our study. Two reviewers extracted data independently and assessed the quality of the retrieved studies, and disagreements were resolved through discussions with a third reviewer. Sensitivities and specificities were pooled by using bivariate diagnostic meta-analysis. We calculated I2 to test the heterogeneity and used meta-regression to identify potential sources of heterogeneity. This systematic review and meta-analysis is registered in international prospective register of systematic reviews (number CRD42020149174).

Results: Six studies with 605 patients were eligible for inclusion. Our meta-analysis produced the following outcomes: the mean sensitivity of IMA in diagnosing acute stroke was 0.80 (95% confidence interval [CI], 0.69-0.88) and the specificity was 0.80 (95% CI, 0.71-0.87). The area under the receiver operating characteristic curve was 0.86 (95% CI, 0.83-0.89), and the pooled diagnostic odds ratio was 16 (95% CI, 8-33). There was obvious heterogeneity between studies (I2 = 78%, 95% CI, 53-100). Sensitivity analysis and meta-regression could account for the heterogeneity.

Conclusion: IMA is a helpful marker for consideration in the early diagnosis of stroke.

Keywords: Diagnosis; Ischaemia; Stroke.

Background: There is still a lack of tools to assess the prognosis of ischemic stroke patients induced by hypertension. In this study, we built a novel prognostic assessment model for ischemic stroke in the Chinese hypertensive population.

Methods: Mass spectrometry technique was used to analyze the changes in serum protein profiles of hypertensive patients with ischemic stroke. A total of 314 hypertensive patients were divided into the testing group (206 patients) and the validation group (108 patients).

Results: Compared with hypertensive patients without ischemic stroke, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), ischemia-modified albumin (IMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), glial fibrillary acidic protein (GFAP), and homocysteine (HCY) levels were significantly increased among hypertensive patients with ischemic stroke (p < 0.05). Then, we built a novel prognostic assessment model for hypertensive patients with ischemic stroke [Logit(P) = 29.172-1.088*CTLA-4-0.952*IMA-0.537*Lp-PLA2 -0.066*GFAP -0.149*HCY]. It showed higher efficiency (AUC = 0.981, sensitivity = 95.5%, specificity = 93.8%) than any single marker. The estimated probability was 0.739, which means if higher than 0.739, it was classified into poor prognosis. Compared with the estimated probability ≤0.739 group, the survival rate of hypertensive patients with ischemic stroke in the estimated probability >0.739 group was significantly decreased (χ² = 40.001, p < 0.001). In the validation group, our novel prognostic assessment model still showed good efficiency (AUC = 0.969, sensitivity = 89.4%, specificity = 92.5%; χ² = 47.551, p < 0.001).

Conclusion: Current novel prognostic assessment model we have built is of great value in the prognostic evaluation for ischemic stroke in the Chinese hypertensive population.

Keywords: hypertension; inflammation; ischemic stroke; mass spectrometry; prognosis.

Background: Pulmonary vascular damage may be associated with oxidative stress in congenital heart diseases. We investigated whether small ventricular septal defects have an effect on the pulmonary bed.

Methods: This prospective cohort study included 100 patients with small ventricular septal defects and 75 healthy controls. Ischemia-modified albumin, high-sensitivity C-reactive protein, and various cardiovascular parameters were assessed in both groups.

Results: The mean ischemia-modified albumin level was significantly higher in patients with small ventricular septal defects (0.62 ± 0.17 absorbance units) than in the control group (0.51 ± 0.09 absorbance units; p < 0.001). The mean high-sensitivity C-reactive protein level was significantly higher in the ventricular septal defects group (3.72 ± 1.57) than in the control group (2.45 ± 0.89; p < 0.001). The ischemia-modified albumin levels in patients with left ventricular internal diameter end diastole and end sistole and main pulmonary artery z-scores ≥ 2 were significantly higher than patients whose z-scores were <2. The ischemia-modified albumin and high-sensitivity C-reactive protein levels were positively correlated in the small ventricular septal defects group (rho = 0.742, p < 0.001). Receiver operating characteristic analyses showed that at the optimal cut-off value of ischemia-modified albumin for the prediction of pulmonary involvement was 0.55 absorbance units with a sensitivity of 60%, specificity of 62% (area under the curve = 0.690, p < 0.001).

Conclusions: We demonstrated the presence of oxidative stress and higher ischemia-modified albumin levels in small ventricular septal defects, suggesting that ischemia-modified albumin might be a useful biomarker for evaluating the effects of small ventricular septal defects on the pulmonary bed.

Keywords: Childhood; ischemia-modified albumin; pulmonary vasculary bed; ventricular septal defect.

Background: Transient ischemic attack (TIA) is a super warning for cerebral infarction stroke, thus probe of sensitive biomarker for TIA diagnosis and prognosis can contribute to make an optimal intervention plan.

Objective: This study was conducted to explore the value of ischemic modified albumin (IMA) and microRNA-12miR-126 on the diagnosis of posterior circulation TIA and the prediction of secondary cerebral infarction.

Study design: This study was conducted as a longitudinal prospective research.

Methods: The levels of serum IMA and miR-126 at 3h, 6h and 12h after TIA onset were analyzed in 106 patients, then the predictive value of IMA and miR-126 for secondary cerebral infarction were tested.

Results: A significant increase of serum IMA and a decrease of miR-126 were observed after TIA onset (P = 0.000),simultaneously a significant negative correlation was found between serum IMA for 3 h and miR-126 for 12 hr=-0.401, P = 0.000. Both IMA and miR-126 were significant associated with the secondary cerebral infarction.

Conclusion: Early detection of IMA and miR-126 is of great value in diagnosing posterior circulation TIA and predicting the secondary cerebral infarction.

Keywords: Ischemic modified albumin; miR-126; posterior circulation transient ischemic attack; secondary cerebral infarction.

Objective: Ischemia-modified albumin (IMA) is a novel marker for the detection of ischemia. The value of this biomarker has been studied in patients with coronary artery disease (CAD). However, the relationship between the severity of coronary stenosis and serum IMA levels remains unknown. Therefore, we aimed to investigate the potential role of serum IMA levels in predicting the severity of coronary atherosclerosis.

Materials and methods: One hundred and forty-two individuals who underwent coronary angiography for coronary artery disease complaints were included in the study. Participants were divided into three groups based on their diagnosis as control (healthy subjects), group I (subjects with lower Gensini score), and group II (subjects with higher Gensini score). Global Registry of Acute Coronary Events (GRACE) risk score and Gensini scores were calculated after coronary angiogram in the patient groups. Then, venous blood samples were collected from each participant. Serum IMA levels and the levels of routine laboratory markers were measured.

Results: The serum lymphocyte, neutrophil, and high-density lipid (HDL) levels were statistically insignificant between the groups. The white blood cell (WBC) count and IMA levels were significantly higher in the patient groups (p < 0.05). The GRACE and Gensini scores were significantly different in the patient groups (p < 0.05). However, there was no significant correlation between the GRACE and Gensini scores and serum IMA levels.

Conclusion: Although IMA levels can be a significant predictor for ischemia according to previous reports, this biomarker seems to be insufficient for determining the severity of disease in patients with CAD.

Keywords: Cardiovascular disease; Coronary artery disease; Disease severity.

Introduction: We investigated the effect of epilepsy on cord blood oxidative stress status.

Material and methods: Thirty (n = 30) pregnant women with epilepsy and thirty (n = 30) healthy controls enrolled in this case control study. Albumin and IMA values and dynamic thiol/disulfide parameters were measured.

Results: Decreased native thiol and total thiol levels were found in the epilepsy group when compared to the control group (p: 0.001, p: 0.002). Higher IMA (p: 0.036) and lower albumin cord levels (P < 0.001) were measured in the epilepsy group with respect to the control group. Apgar scores at 1 and 5 miutes were lower in the epilepsy group (respectively; p = 0.012, p = 0.010). A negative correlation was found between IMA and cord pH value (r = 0.288 p = 0.034).

Conclusion: This study showed that epilepsy may alter thiol disulfide homeostasis and IMA levels.

Keywords: Epilepsy; albumin; ischemia modified albumin; oxidative stress; thiol-disulfide homeostasis.

Introduction: To assess the effect of hormone therapy (HT) on serum ischemia modified albumin (IMA) levels in healthy menopausal women.

Material and methods: Thirty surgical menopausal women who were admitted to our menopausal polyclinic during a 1-year period and diagnosed with menopause and planned to have HT for menopausal symptoms were enrolled in this prospective study. The serum İMA levels were recorded before and after (3 months, 6 months, 12 months later) hormone treatment (2 mg estradiol hemihydrate).

Results: The mean age of women was 47.60 ± 2.34 years. The mean serum IMA levels were 0.610 ± 0.096 absorbance units (ABSU) at the beginning and 0.484 ± 0.080 ABSU after 3 months of hormone therapy. Following 6 months of hormone therapy, serum IMA level was 0.546 ± 0.075, and reached 0.580 ± 0.089 ABSU following 12 months of therapy.

Conclusions: These findings suggest that HT may not block the menopause induced ischemia process. Although HT had a positive effect on serum IMA levels following 3 months' use, serum IMA levels returned to baseline levels after 12 months' use. Based on this study's findings, long-term use of HT may not have a positive effect on cardiovascular disease protection.

Keywords: IMA; cardiovascular risk; hormone therapy; menopause.

Aim: Trauma is the most common cause of death in childhood. Tissue damage, ischemia-reperfusion injury, and inflammatory response are mainly responsible for increasing free oxygen radicals. In this study, we aimed to investigate the use of thiol-disulfide and ischemia-modified albumin levels as a diagnostic laboratory parameter in trauma children.

Methods: Of 202 children, 101 were hospitalized in the pediatric surgical intensive care unit with trauma, and 101 others were healthy children. Levels of native thiol (-SH), total thiol (SH + SS), dynamic disulfide (SS), dynamic disulfide (SS) / total thiol (SH + SS), albumin, and ischemic modified albumin (IMA) were measured from the sera of patients and healthy volunteers. For statistical analyses, SPSS 17,0 was used. Mann-Whitney U and paired correlation tests were used where appropriate. p <0.05 was considered significant.

Results: The mean age of the patients in the trauma group (Boys: 61 Girls: 40) was 7,88 years and the control group was 8,00 years. In the trauma group, 86 of children were exposed to blunt trauma, 15 children had penetrating trauma and 54 patients had multiple trauma. Surgical procedures were performed on 17 patients. In the trauma group, native thiol, total thiol, dynamic disulfide / total thiol, albumin and IMA levels were significantly lower than that of the control (p <0.001), and their dynamic disulfide (p = 0.001) was higher compared to the control. There was no difference thiol-disulfide parameters in trauma groups sub-division as surgery(n=17) vs. follow-up(n=84) groups or multiple trauma(n=54) vs. isolated organ trauma(n=47) groups, or penetrating(n=15) or blunt trauma(n=86) groups.

Conclusion: Thiol-disulfide balance and IMA levels show changes in favor of oxidative stress in children with trauma, however, it cannot be used as a laboratory marker that helps to show the system and organ affected by the trauma and to decide the surgical intervention.

Keywords: children; ischemia-modified albumin; oxidative stress markers; thiol-disulfide; trauma.

Purpose: In this study, we evaluated the total antioxidant capacity, nitrosative stress, and protein/DNA oxidation and glycoxidation products in patients with colorectal cancer regarding histopathological parameters associated with the tumour microenvironment, such as inflammatory infiltration and tumour budding and compare all determined parameters between tumours located in the right and left side of the colon and normal mucosa.

Patients and methods: Ferric reducing antioxidant power (FRAP), nitrosative stress (myeloperoxidase (MPO), nitrogen oxide (NO), peroxynitrite, and nitrotyrosine), protein oxidation products (protein carbonyls (PC), total thiols, and ischemia modified albumin (IMA)), protein glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, Amadori product, advanced glycation end products (AGE)) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in homogenates from normal and cancerous tissue of 30 patients with colorectal cancer.

Results: Levels of FRAP (p=0.0009), IMA (p=0.0002), kynurenine (p<0.0001), N-formylkynurenine (p<0.0001), dityrosine (p<0.0001), Amadori products (p=0.0024), AGE (p<0.0001), MPO (p<0.0001), NO (p<0.0001) and nitrotyrosine (p=0.0011) were increased, whereas PC (p=0.0004), tryptophan (p<0.0001), 8-OHdG (p<0.0001) and peroxynitrite (p=0.0003) were decreased in the left-side tumour compared to the right-side tumour and normal mucosa.

Conclusion: Our results showed that colorectal cancer is related with disturbances in antioxidant defense and increased oxidative and nitrosative damages to proteins and DNA. These parameters may be useful for evaluation the progression and differentiation of the tumour location. We also demonstrated that redox indicators may depend on the histological type of the tumour and may influence tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion, inflammatory infiltration, and tumour budding, which are part of the tumour microenvironment.

Keywords: colorectal cancer; nitrosative stress; oxidative stress; redox biomarkers.

Albumin is one of the most abundant proteins in the body of mammals: about 40% of its pool is located in the intravascular space and the remainder is found in the interstitial space. The content of this multifunctional protein in blood is about 60-65% of total plasma proteins. A decrease in its synthesis or changes of functional activity can destabilize oncotic blood pressure, cause a violation of transporting hormones, fatty acids, metals, and drugs. Albumin properties change under ischemic attacks associated with oxidative stress, production of reactive oxygen species, and acidosis. Under these conditions, ischemia-modified albumin (IMA) is generated that has a reduced metal-binding capacity, especially for transition metals, such as copper, nickel, and cobalt. The method of determining the cobalt-binding capability of HSA was initially proposed to evaluate IMA level and then licensed as an ACB test for routine clinical analysis for myocardial ischemia. Subsequent studies have shown the viability of the ACB test in diagnosing other diseases associated with the development of oxidative stress. This review examines recent data on IMA generation mechanisms, describes principles, advantages, and limitations of methods for evaluation of IMA levels, and provides detailed analysis of its use in diagnostic and monitoring therapeutic efficacy in different diseases.

Objective: Coronary artery bypass grafting (CABG) represents the significant source of increased oxidative stress (OS). We aimed to follow the OS status parameters (i.e., ischemia-modified albumin (IMA), malondialdehyde (MDA), superoxide anion, prooxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), and superoxide-dismutase (SOD)) change through the predefined study times in two different surgical procedures, i.e., cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting (OPCAB). Additionally, we aimed to investigate those OS status parameters in specific study times according to SYNTAX score (SS), an established angiographic score for evaluating the extensity and severity of coronary artery disease. Patients and Methods. A total of 107 patients that were planned to undergo CABG were included (i.e., 47 patients in OPCAB and 60 patients in CPB group). Blood samples were taken at 6 time intervals: before surgery (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after termination of the operation (t6).

Results: IMA levels were higher in CPB than that in OPCAB baseline and rose in CPB group in t2 point. TOS decreased in both study groups, compared to baseline values, but without statistical significance. Superoxide anion and PAB significantly increased in t3-t6 study times, in both groups. MDA significantly increased only in CPB group in t5 and t6 interval. MDA was significantly higher in CPB group compared to OPCAB in t6 study point. CPB patients had significantly lower TAS compared to OPCAB patients at the beginning and in t2 and t3 study points. They also had significantly lower SOD activities compared to OPCAB, baseline, and in several study points. Moreover, TAS, SOD, and TAS/TOS ratio were significantly lower, whereas PAB and TOS/TAS were significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of high SS.

Conclusion: CPB patients were in more severe ischemia baseline than OPCAB group and IMA rose in CPB patients immediately after the surgery end, but not later. Also, the antioxidant status was significantly lower, whereas the prooxidant status was significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of CAD (as determined with SS), showing that SOD and IMA had very good discriminatory capability towards higher SS status.

Objective: To investigate the relationship between thyroid functions and asymmetric dimethylarginine (ADMA), ischemia-modified albumin (IMA), and other metabolic laboratory markers in euthyroid adults and whether narrower thyroidal targets are required for lower metabolic risk.

Materials and methods: Thyroid functions, antithyroid autoantibodies, and metabolic parameters were measured for 115 patients. Forty-seven had autoimmune thyroiditis (AIT). Analyses were performed according to cutoff values of 1, 2, 2.5, and 3 mIU/L for thyrotropin, 0.84 ng/dL for free thyroxine (fT4), and 3.59 ng/dL for free tri-iodothyronine (fT3).

Results: There was no relationship between thyrotropin and fT3 cutoff values and metabolic parameters. Only C-reactive protein was lower in the group with thyrotropin ≤2.5 μIU/L. A weak positive correlation was found between fT4 with IMA and IMA corrected for albumin (r = 0.187, P = .05; r = 0.204, P = .034, respectively). There was no difference between AIT and the metabolic laboratory parameters examined in the study.

Conclusion: This study is the first to evaluate ADMA in AIT. Narrower thyroid function targets are not required for better metabolic control in euthyroid adults.

Keywords: asymmetric dimethylarginine; autoimmune thyroiditis; euthyroid; ischemia-modified albumin; metabolic; risk.

Purpose: This study aimed to determine the potential clinical use of dynamic thiol-disulfide balance in cases with preinvasive lesions of the cervix.

Methods: One hundred and sixteen patients with high-grade squamous intraepithelial lesion, 100 patients with low-grade squamous intraepithelial lesion, and 110 healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, and oxidative stress index of the retrieved cases were further analyzed.

Results: Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p: 0.004 and 0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p: 0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p: 0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p: 0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r: 0.420, p < 0.001).

Conclusion: The analysis of dynamic thiol-disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus-related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol-disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer.

Keywords: Cervical preinvasive lesion; Disulfide; Disulfide homeostasis; Oxidative stress; Squamous intraepithelial lesion; Thiol.

Objective: The purpose of this study is to evaluate antioxidant balance in pregnant women with meconium-stained amniotic fluid.

Methods: Forty pregnant women with meconium-stained amniotic fluid and 40 pregnant women with non-meconium-stained amniotic fluid were included in the study. By checking the ischemia modified albumin (IMA) level and thiol/disulfide homeostasis in the maternal blood during labor and in newborn umbilical cord blood at the first minute after birth, antioxidant/oxidant balance was evaluated.

Results: No statistically significant difference was found between the maternal albumin levels. Maternal IMA level was statistically significantly higher in the meconium group than in the control group (p = .045). Maternal native thiol (SH) and maternal total thiol levels were statistically significantly higher in the control group than in the meconium group (p = .042 and p = .009, respectively). No statistically significant difference was found between maternal disulfide/native thiol (p = .262), maternal disulfide/total thiol (p = .152), maternal native thiol/total thiol (p = .153) rates in both groups. No statistically significant difference was determined between the patients with meconium and the control group in terms of cord blood IMA (p = .474), Albumin levels (p = .664), cord blood Native thiol (p = .944), cord blood total thiol (p = .612) levels and cord blood disulfide/native thiol (p = .240), cord blood disulfide/total thiol (p = .276), cord blood native thiol/total thiol (p = .277) rates.

Conclusion: Determination of a decrease in SH and Total Thiol levels in maternal serum and an increase in the meconium group's IMA level was interpreted as a shift of antioxidant balance toward oxidant in this group.

Keywords: Meconium; native thiol; oxidative stress; thiol/disulfide.

Objective: To investigate the value of ischemia modified albumin (IMA) level for predicting in-hospital mortality in patients with acute aortic dissection (AAD). Methods: A total of 195 patients with AAD from the Department of Cardio-Vascular Surgery of Affiliated Hospital of North Sichuan Medical College from January 2017 to November 2019 were consecutively collected, with 126 males and 69 females. Based on whether they died during hospitalization or not, these patients were divided into 2 groups: survival group and mortality group. The baseline data and IMA levels at admission of the two groups were recorded. Univariate logistic regression analysis was used to identify the independent risk factors, and multivariate logistic regression analysis was further performed on variables with statistical significance in univariate analysis. The area under the receiver operating characteristic (ROC) curve was calculated to determine the value of IMA for predicting in-hospital mortality in patients with AAD. Results: Forty-two AAD patients died and 153 survived, and the mortality rate was 21.5%. Logistic regression analysis showed that age (OR=CI:1.247-4.826,P=OR=CI:3.189-14.291,P<0.001), drug therapy (OR=CI:2.463-10.700,P<0.001), IMA level (OR=CI:2.231-8.953,P=OR=CI:0.093-0.406,P<0.001). The area under the ROC curve for IMA level in predicting in-hospital mortality with AAD was 0.838 (95%CI: 0.774-0.901, P<0.001), with a cut-off value of 86.55 U/ml, and the sensitivity and specificity were 83.3% and 75.2%, respectively. Conclusions: IMA may serve as a simple risk assessment indicator for patients with AAD. IMA level at admission is an independent predictor of in-hospital mortality. For patients with higher IMA level, early surgical intervention should be performed.

目的： 探讨缺血修饰白蛋白（IMA）对急性主动脉夹层（AAD）患者院内死亡的预测价值。 方法： 连续收集2017年1月至2019年11月因AAD在川北医学院附属医院心脏大血管外科救治的195例患者的临床资料，其中男126例，女69例；按照患者住院期间是否死亡分为生存组和死亡组，分别记录两组患者的基本资料及入院时IMA水平；将单因素分析具有统计学意义的变量进行多因素logistic回归分析，采用受试者工作特征（ROC）曲线计算ROC曲线下面积（AUC），以评估IMA对AAD患者住院期间全因死亡的预测价值。 结果： 本组AAD患者院内全因死亡42例，存活153例，死亡率为21.5%；多因素logistic回归分析结果显示：年龄（OR=CI：1.247~4.826，P=OR=CI：3.189~14.291，P<0.001）、药物治疗（OR=CI：2.463~10.700，P<0.001）及IMA水平（OR=CI：2.231~8.953，P=OR=CI：0.093~0.406，P<0.001）。IMA预测AAD患者院内死亡的AUC为 0.838（95%CI：0.774~0.901，P<0.001），最佳截断值为86.55 U/ml，灵敏度为83.3%，特异度为75.2%。 结论： IMA可对AAD患者进行危险评估，入院时IMA水平是AAD患者院内死亡的独立危险因素；对于IMA水平较高者，应及早进行手术干预。.

Objective: The role of protein oxidation in the development of diabetic microvascular complications was investigated.

Methods: In total, 266 participants were split into five groups: Group 1; diabetes mellitus for at least 10 years without any complications, Group 2; diabetic nephropathy, Group 3; diabetic neuropathy, Group 4; diabetic retinopathy, and Group 5; control group. Thiol, disulfide, ferroxidase, and ischemia-modified albumin (IMA) levels were analyzed in the serum.

Results: Native thiol, total thiol, and native thiol/total thiol were lower in Group 4 than Groups 1, 3, and 5 (p<0.001). However, disulfide/native thiol and disulfide/total thiol were higher in Group 4 than all other groups (p<0.001). IMA was higher in Groups 3 and 4 than all other groups (p<0.001). Ferroxidase was lower in Groups 3 and 4 than Group 2 (p<0.001).

Conclusion: Thiol-disulfide homeostasis impairment in favor of disulfide may have a function in the progress of diabetic retinopathy. Furthermore, the disruptions of IMA and ferroxidase levels involve in the development of diabetic retinopathy and neuropathy.

Keywords: Diabetes mellitus; microvascular complications; neuropathy; retinopathy; thiol-disulfide.