Antra Jurka

The Relationship Between Maximal Exercise-Induced Increases in Serum IL-6, MPO and MMP-9 Concentrations

The aim of this study was to test the hypothesis that exercise would induce inflammatory response characterized by increased pro‐inflammatory cytokines – interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α), adhesion molecule, matrix metalloprotease‐9 (MMP‐9) and myeloperoxidase (MPO) levels. Additional aim was to elucidate the possible source of maximal exercise‐induced increase in MMP‐9 concentration. To examine our hypothesis, 26 professional male ice hockey players [age 25 ± 1 (mean ± SEM) years; BMI 25.8 ± 0.4 kg/m2] performed an incremental bicycle test until exhaustion, when maximal oxygen consumption was recorded. Venous blood samples were collected 30 min before and 2 min after exercise. There was an increase in the count of leucocytes (8.7 ± 1.8 versus 5.7 ± 1.3 × 109 cells per l) and IL‐6 (1.24 ± 0.17 versus 0.69 ± 0.13 pg/ml), MPO (72 ± 7 versus 50 ± 4 ng/ml) and MPP‐9 (139 ± 9 versus 110 ± 6 ng/ml) concentrations (P < 0.05) comparing post‐ and pre‐exercise levels. Maximal exercise‐induced increase in MPO correlated with the increases in IL‐6 (P < 0.05, R = 0.54) and MMP‐9 (P < 0.01, R = 0.62) concentrations. Furthermore, increase in IL‐6 correlated with the increase in MMP‐9 concentrations (P < 0.05, R = 0.60). Maximal exercise induces an inflammatory response characterized by leucocytosis and increased IL‐6, MPO and MMP‐9 concentrations. Correlations between increased MPO (marker of neutrophils degranulation) and both increased IL‐6 and MMP‐9 concentrations may suggest that neutrophils could be the main source of these inflammatory biomarkers during maximal exercise. Furthermore, correlation between increases in serum IL‐6 and MMP‐9 concentrations may suggest that IL‐6 could exert modulatory effects on MMP‐9 release during maximal exercise.

Circulating adhesion molecules, matrix metalloproteinase-9, plasminogen activator inhibitor-1, and myeloperoxidase in coronary artery disease patients with stable and unstable angina

BACKGROUND There are many pathophysiological mechanisms underlying reciprocal relationships between changes in cytokines and insulin resistance in metabolic and cardiovascular disorders. The aim of this study was to evaluate alterations in soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), matrix metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase (MPO) levels, and their relation to insulin resistance in coronary artery disease (CAD) patients with stable and unstable angina (SAP, UAP). METHODS Non-diabetic CAD patients were classified into two groups: 22 patients with SAP and 22 patients with UAP. 22 healthy subjects were selected as controls. The study groups were matched for age and sex. Insulin resistance was evaluated by HOMA-IR method. Serum levels of sICAM-1, sVCAM-1, sE-selectin PAI-1(total), MPO and MMP-9 were quantified by xMAP technology (Luminex-200 analyzer). RESULTS Both patient groups demonstrated significantly elevated serum levels of sICAM-1, sE-selectin, PAI-1(total), MPO and MMP-9 (p<0.05) as well as higher IR-HOMA values (p<0.05) than those of healthy controls. The elevation was more pronounced in the UAP group (p<0.01). HOMA-IR was correlated with sICAM-1, PAI-1(total), and MMP-9 (p<0.01). CONCLUSION Our findings show that CAD patients have elevated HOMA-IR values. Furthermore, CAD patients with UAP have higher levels of sICAM-1, sVCAM-1, sE-selectin, MMP-9, PAI-1(total), and MPO than patients with SAP, and there are relationships between three of the above biomarkers: sICAM-1, PAI-1(total), MMP-9 and HOMA-IR.

Relation of inflammatory chemokines to insulin resistance and hypoadiponectinemia in coronary artery disease patients

BACKGROUND Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither. METHODS CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology. RESULTS Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01). CONCLUSION Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.

Role of serum cytokines in acute appendicitis and acute mesenteric lymphadenitis among children

BACKGROUND AND OBJECTIVE The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). The aim of this study was to evaluate differences in cytokine levels between AA and AML. MATERIALS AND METHODS Data of 7- to 18-year-old children were collected prospectively from October 2010 to October 2013. There were 31 patients with AA (AA group), 26 with AML (AML group), and 17 with elective non-inflammatory surgical disease (control group). Serum levels of IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α and white blood count (WBC) were measured three times consecutively in each group. RESULTS The level of IL-6 and IL-10 was significantly higher in the AA group than the AML group at the first measurement (8pg/mL vs. 3.2pg/mL, P=0.000; 6.1pg/mL vs. 3.2pg/mL, P=0.005, respectively). There was a significant difference observed in time dynamics of concentration of IL-6 and MCP-1 for AA and AML. The area under the curve (AUC) was 0.77 (95% CI 0.64-0.89; P=0.001) for IL-6 with a cut-off value of 4.3pg/mL (67.7% sensitivity and 76.9% specificity) for AA 1h before surgery. The AUC for WBC was 0.72 (95% CI 0.58.4-0.85; P=0.005) with a cut-off value of 10.7×103/μL (sensitivity 71.0% and specificity 46.2%). CONCLUSIONS Serum IL-6 with a cut-off value of 4.3pg/mL and WBC with a cut-off value of 10.7×103/μL assessed together will yield more sensitivity for AA.

Nitric Oxide Production and Arachidonic Acid Metabolism in Platelet Membranes of Coronary Heart Disease Patients with and without Diabetes

Aim: To evaluate the levels of nitrite (NO–2) and nitrate (NO–3) ions and the incorporation of [3H]arachidonic acid (AA) into phospholipids of platelet membranes from coronary artery disease (CAD) patients with and without diabetes (NIDDM). Subjects and Methods: Eighteen CAD patients (group A), 18 CAD patients with NIDDM (group B), and 20 healthy controls (group C) without dyslipidemia, peripheral vascular disease and hypertension were included in the study. The groups were matched for age, sex and body mass index. The diagnosis of CAD was confirmed by coronary angiography. The nitric oxide end products (NOx), NO–2 plus NO–3 ions in platelet membranes, were determined using a spectrophotometric method based on the Griess reaction. The turnover of phospholipids was evaluated by incorporation of [3H]AA into platelet membrane phospholipids. Results: A significantly smaller amount of NOx ions was in the platelet membrane of groups A (40 ± 8 µmol/l) and B (29 ± 10 µmol/l) than C (57 ± 6 µmol/l), p < 0.001. Conversely a significantly greater amount of [3H]AA was incorporated into platelet phospholipids of group B patients (5,123 ± 1,637 dpm/mg) than groups A (3,159 ± 1,253 dpm/mg; p < 0.002) and C (1,621 ± 417 dpm/mg). An inverse correlation between [3H]AA incorporation and NOx levels was established: r = –0.76 (p < 0.05, n = 36) in CAD patients. Conclusions: Diabetes in CAD patients decreased the ability to produce platelet-derived NO and affects AA metabolism. This may result in higher platelet sensitivity to aggregating stimuli.

Influence of hydrogen ion concentration on refractive index value in red blood cells of diabetes patients

Since hyperglycaemia changes fluidity of erythrocyte cell membrane and impair cell deformability, our goal was to characterize light refractive properties of haemoglobin and red blood cells (RBC) in diabetes patients. Microscopic investigation was carried out on intact and in methanol fixed RBCs of diabetes patients with long-term hyperglycaemia (glycosylated haemoglobin > 7,5%). Interference microscopy was used for refractive index (RI) measurements at 18 different pH levels in range of 2 - 13. Results showed that the curves of RI in intact and fixed cells of diabetes patients and fixed cells for control group were of similar configuration, with one branch in alkaline portion, one branch in acidic portion, and two minima and a maximum in neutral portion of pH scale. The curves of RI of intact cells of the control group were with one minimum in the neutral portion of pH scale. The curves of the individuals from the control group overlapped each other (maximum for fixed cells is at pH equals 6,3; minimum for intact cells at pH equals 7,2). On the contrary, curves of RI in RBC of diabetes patients were not uniform in the neutral portion and alkaline portion (maximum for fixed and intact cells at pH equals 6,9). The curves of RI in RBC of diabetes patients in the neutral zone was shifted towards the alkaline end of the pH scale, and the curves of RI of RBC were lower compared to the control curves.

Changes in Serum High-Molecular-Weight Adiponectin Levels in Critically Ill Children with Systemic Inflammatory Response Syndrome

Background: The aim of the study was to evaluate the effect of the systemic inflammatory response syndrome (SIRS) on serum high-molecularweight adiponectin (HMWA) levels. Method:

Different Cytokine Profiles in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis / Atðíirîga Citokînu Grupas Seruma Iekaisuma Mediatoru Izpausme Akûta Apendicîta Un Akûta Mezenteriâla Limfadenîta Gadîjumâ Bçrniem

Abstract The aim of this study was to investigate the role of serum cytokines in the diagnosis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). Data were collected prospectively on 7 to 18 year old children (October 2010 - October 2013): 31 patients with AA, 26 patients with AML, and 17 patients with elective non-inflammatory surgical disease were selected as controls. Serum levels of IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α were measured. Patients with AA had significantly increased serum levels of IL-6(1) (z = -3.72; p = 0.0002) and IL-10(1) (z = -2.81; p = 0.005) compared to AML before any treatment. The consecutive measurements of MCP-1 in serum demonstrated a significant difference within 72 hours in the AA group (Wilks’ Lambda test 0.80; F(2;29) = 3.5; p = 0.04) and also in the AML group (Wilks’ Lambda test 0.70; F(2;24) = 5.0; p = 0.01). The increased values of IL-6 and IL-10 were the most reliable cytokines one hour before surgical intervention for patients with AA. MCP-1 values changed significantly within 72 hours after patient hospitalisation but did not differ between the groups, and could not be a helpful serum biomarker in distinguishing patients with AA and AML.

TNF-α And IL-8 As Prognostic Markers of Birth Outcome in Overweight and Non-Overweight Pregnant Women

Summary Introduction. Overweight has become a major risk factor for various diseases. Compared with normal weight overweight pregnant women have an increased risk of various complications in childbirth - invasive fetal monitoring, perineal ruptures, operative vaginal deliveries, cesarean sections, increased gestational age at delivery, and increased maternal length of stay are present. Both pregnancy and childbirth is a conditions significantly affected by the the immune system. However, this relationship and the possibility of its practical use is still not fully explored. Aim of the study. Our aim is to determine whether overweight have the same impact on obstetrical outcome as obesity, explore changes of Interleukin-8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α) levels in the first and second trimester of pregnancy, compare these changes in normal weight pregnant women and pregnant women with overweight, to clarify their relationship to pregnancy outcome and to determine whether these cytokines have the potential to serve as biomarkers for prediction of labor complications. Material and methods. This was a prospective, longitudinal study were we enrolled 55 pregnant women in their first antenatal visit. Blood samples were taken at different weeks of pregnancy. TNF-α and IL-8 concentrations were measured by Luminex xMAP technology (Luminex Corporation). Statistical analysis was performed using LibreOffice Calc, the Fisher exact test, Ttest, Spearman’s rank correlation coefficient and a non-parametric Mann-Whitney-Wilcoxon test. For all statistical analyses, p<0.05 was considered statistically significant. Results. Labor dysfunction and cesarean section were more frequently observed in women with high BMI. In cases of vaginal delivery ruptures were more often for patients in high BMI group but the difference is small. Although average birth weight was slightly lower in normal BMI group, the difference is not statistically significant (p=0.13). Male gender babies were more often for women with high BMI, but statistical difference is not significant (p=0.15). Comparing the levels of TNF-α and IL-8 in different weeks of pregnancy no statistically significant difference between the study groups was found. There was no strong tendencies in dynamics in TNF-α and IL-8 levels in differend first and second trimester weeks of pregnancy. No statistically significant differences in levels of TNF- α and IL-8 depending on the fetal macrosomia were observed, but IL-8 level correlated with labour dysfunction and mode of delivery. Conclusions. Overweight is a risk factor for labor dysfunction and probability of CS. TNF-α and IL-8 levels in early pregnancy does not differ in women with and without elevated BMI. In first and second trimesters of pregnancy no dynamics in TNF-α and IL-8 levels in maternal serum is observed. IL-8 level in the second trimester is correlated with labour dysfunction and increased cesarean section risk. This is an important finding, but its clinical value still requires further research.

Neopterin, cellular adhesion molecules and myeolperoxidase in patients with stable and unstable angina pectoris

Neopterin, cellular adhesion molecules and myeolperoxidase in patients with stable and unstable angina pectoris Recent data indicate that the serum level of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, is elevated in patients with acute coronary syndrome (ACS) and seems to be a prognostic marker for major cardiovascular events. Soluble cellular adhesion molecules (sCAMs) and myeloperoxidase (MPO) levels are also related to ACS. The aim of the present study was to evaluate differences in serum levels of neopterin, sCAMs and MPO between coronary artery disease and metabolic syndrome (CAD-MetS) patients with stable and unstable angina pectoris (SAP, UAP), and to clarify the relationships between neopterin and other biomarkers. The study included 60 patients with CAD-MetS who were classified into two groups, 30 patients with SAP and 30 patients with UAP. Twenty healthy subjects were selected as controls (C). Serum soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and MPO levels were measured by Luminex xMAP technology, and serum neopterin concentrations were measured by radioimmunoassay. Results: Serum levels of neopterin, MPO, sVCAM-1, sICAM-1, and sE-selectin were significantly higher in patients with UAP in comparison with the group of healthy controls (P < 0.05). Patients with SAP also had higher levels of these biomarkers than those in healthy controls (P < 0.05), except for sE-selectin. The biomarker level did not differ between the two patient groups, except for MPO, which was significantly higher in the USP group (P < 0.05). Neopterin was significantly correlated only with sVCAM-1 (P < 0.05). In conclusion, CAD-Met patients with SAP had more apparent raised levels of serum sICAM-1 and sVCAM-1, simultaneously with higher MPO and neopterin concentrations, in comparison to those in healthy subjects. However, UAP is also associated with more substantial changes in MPO and significantly increased sE-selectin levels. Neopterin concentration was had a close correlation only with sVCAM-1. Neopterīns, šūnu adhēzijas molekulas un mieloperoksidāze pacientiem ar stabilu un nestabilu stenokardiju Mūsdienu pētījumi liecina, ka pacientiem ar akūtu koronāro sindromu (ACS) ir palielināta neopterīna koncentrācija asins serumā un tā spēj kalpot kā prognostisks biomarķieris kardiovaskulāriem notikumiem. Seruma šķīstošo šūnu adhēzijas molekulu (sCAMs) un mieloperoksidāzes (MPO) koncentrācijas palielināšanās arī ir saistīta ar ACS. Šī pētījuma mērķis bija novērt¯t atšķirības neopterīna, sCAMs un MPO seruma koncentrāciju atšķirības koronārās sirds slimības un metabolā sindroma pacientiem (CAD-MetS) ar stabilu un nestabilu stenokardiju (SAP, UAP), kā arī noskaidrot neopterīna saistību ar minētajiem biomarķieriem. Pētījumā tika iesaistīti 60 CAD-MetS pacienti, no kuriem 30 bija ar SAP un 30 ar UAP. 20 veseli voluntieri tika iekļauti kontroles grupā (C). Seruma šķīstošo vaskulāro šūnu adhēzijas molekulu-1 (sVCAM-1), intracelulāro šūnu adhēzijas molekulu-1(sICAM-1), šķīstošā E-selektīna (sE-selectin) un MPO koncentrācijas tika noteiktas ar Luminex xMAP tehnologiju, bet seruma neopterīna koncentrācija - radioimunologiski. Seruma neopterīna, MPO, sVCAM-1, sICAM-1 un sE-selectin koncentrācijas bija statistiski ticami augstākas pacientiem ar UAP, salīdzinot ar C grupu (P < 0.05). Pacientiem ar SAP arī bija būtiski augstāka minēto biomarķieru koncentrācija serumā nekā veseliem voluntieriem, izņemot sE-selectin koncentrācijas, kas neatšķīrās. Pētījuma biomarķieru koncentrācijas neatšķīrās starp pacientu grupām, izņemot MPO koncentrāciju, kas bija būtiski lielāka USP pacientu grupā (P < 0.05). Neopterīna koncentrācijas būtiski korelēja tikai ar sVCAM-1 koncentrācijām (P < 0.05). Tādējādi CAD-MetS pacientiem ar SAP ir būtiskāk izteikts sVCAM-1 un sICAM-1 seruma koncentrāciju palielinājums, vienlaikus, lielākas neopterīna un MPO koncentrācijas, bet UAP saistīts ar vēl būtiskāku MPO un sE-selectin koncentrāciju palielināšanos, salīdzinot ar veseliem voluntieriem. Seruma neopterīnam ir cieša korelācija tikai ar sVCAM-1.