Activation of TF-Dependent Blood Coagulation Pathway and VEGF-A in Patients with Essential Thrombocythemia.

Background and objectives: Recent studies suggest that a vascular endothelial growth factor (VEGF-A) may be involved in the thrombotic process by stimulating the expression of tissue factor in vascular endothelial cells. Tissue factor (TF) can also stimulate the transcription of the gene encoding VEGF-A. The relationship between coagulation and angiogenesis in myeloproliferative neoplasms is not fully understood. The aim of this study was to evaluate the concentration of TF in relation to VEGF-A in the blood of patients with essential thrombocythemia (ET). Patients and methods: The study group consisted of 130, newly diagnosed patients with ET (mean age 61 years). The control group consisted of 35 healthy volunteers (mean age 51 years). Concentrations of VEGF-A, TF, and tissue factor pathway inhibitor (TFPI) were analysed using immunoenzymatic methods. TF and TFPI activities were performed using chromogenic assays. Results: The median concentration of TF Ag was 3-fold higher and the TF activity was more than 15-fold higher in ET patients than in normal individuals. There were no statistically significant differences in the TFPI concentration and activity between groups. VEGF-A was significantly increased in patients with ET (p < 0.000001). Analysis of correlations revealed a positive correlation between VEGF-A and TF Ag as well as a positive correlation between VEGF-A and TFPI activity. Conclusions: The simultaneous increase of TF concentration and activity, VEGF-A in the blood of patients with ET, as well as a positive correlation between the concentration of TF and VEGF-A demonstrates the coexistence of TF-dependent coagulation and activation of angiogenesis.

VEGF-A, sVEGFR-1, and sVEGFR-2 in BCR-ABL negative myeloproliferative neoplasms.

BACKGROUND AND OBJECTIVE: Data from the literature indicate the relationship between the bone marrow microvessel density and the blood parameters of angiogenesis. The aim of this study was to evaluate selected parameters of angiogenesis (VEGF-A, sVEGFR-1, and sVEGFR-2) and their correlations with white blood cells, platelets, and red blood cells. MATERIALS AND METHODS: The study included 72 patients (mean age, 61.84 years) with myeloproliferative neoplasms (MPNs): essential thrombocythemia (ET) (n=46), polycythemia vera (PV) (n=19), and primary myelofibrosis (PMF) (n=7). Serum VEGF-A, sVEGFR-1, and sVEGFR-2 were determined using the ELISA assay. RESULTS: We observed a significantly higher level of VEGF-A and reduced concentrations of sVEGFR-1 and sVEGFR-2 in the whole group of patients with MPNs as compared to controls. Detailed analysis confirmed significantly higher level of VEGF-A and lower concentration of sVEGFR-2 in each subgroups of MPNs patients. However, sVEGFR-1 concentrations were significantly lower only in PV and ET patients. CONCLUSIONS: The study showed an increased level of VEGF-A, which may indicate the intensity of neoangiogenesis in the bone marrow. Decreased sVEGFR-1 and sVEGFR-2 in the blood of patients with MPNs may reflect consumption of these soluble receptors.

CEBPA copy number variations in normal karyotype acute myeloid leukemia: Possible role of breakpoint-associated microhomology and chromatin status in CEBPA mutagenesis.

Copy number variations (CNV) in CEBPA locus represent heterogeneous group of mutations accompanying acute myeloid leukemia (AML). The aim of this study was to characterize different CEBPA mutation categories in regard to biological data like age, cytology, CD7, and molecular markers, and identify possible factors affecting their etiology. We report here the incidence of 12.6% of CEBPA mutants in the population of 262 normal karyotype AML (NK-AML) patients. We confirmed that double mutant AMLs presented uniform biological features when compared to single CEBPA mutations and accompanied mostly younger patients. We hypothesized that pathogenesis of distinct CEBPA mutation categories might be influenced by different factors. The detailed sequence analysis revealed frequent breakpoint-associated microhomologies of 2 to 12bp. The analysis of distribution of microhomology motifs along CEBPA gene showed that longer stretches of microhomology at the mutational junctions were relatively rare by chance which suggests their functional role in the CEBPA mutagenesis. Additionally, accurate quantification of CEBPA transcript levels showed that double CEBPA mutations correlated with high-level CEBPA expression, whereas single N-terminal CEBPA mutations were associated with low-level CEBPA expression. This might suggest that high-level CEBPA expression and/or accessibility of CEBPA locus contribute to B-ZIP in-frame duplications.

Soluble Hemojuvelin and Ferritin: Potential Prognostic Markers in Pediatric Hematopoietic Cell Transplantation.

OBJECTIVE: Iron overload (IO) is a common and life-threatening complication resulting from the therapy of AL and HCT patients. This study aimed to evaluate the prognostic value of 12 serum biomarkers of iron metabolism in pediatric patients treated for AL or undergoing HCT. PATIENTS: Overall, 50 patients with AL after intensive treatment and 32 patients after HCT were prospectively included in the study. AL patients at diagnosis and healthy controls served as reference groups. METHODS: The impact of the following 12 serum iron metabolism parameters on the outcome of AL/HCT patients was analyzed: iron, transferrin (Tf), total iron-binding capacity (TIBC), ferritin, ferritin heavy chains (FTH1), ferritin light chains (FTL), hepcidin, soluble hemojuvelin (sHJV), soluble ferroportin-1 (sFPN1), erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR). RESULTS: With a median follow-up of 2.2 years, high levels of ferritin and low levels of sHJV had an adverse prognostic impact on OS and EFS in children after HCT. If these patients were combined with those with AL after intensive chemotherapy, the results were confirmed for OS and EFS both for ferritin and sHJV. CONCLUSIONS: Among the 12 analyzed serum parameters of iron metabolism, increased levels of ferritin and decreased levels of sHJV had an adverse prognostic impact on survival in children after HCT. More data are needed to clarify the relationship between ferritin, sHJV, and mortality of AL children after intensive chemotherapy, and more extensive prospective studies are required to prove sHJV predictivity.

The influence of selected demographic factors and wound location on the concentration of vascular endothelial growth factor (VEGF-A) in the wound healing process after neurosurgery: brief report.

The main aim of the work was to estimate the influence of selected demographic factors and wound location on the concentration of the vascular endothelial growth factor (VEGF-A) in patients after neurosurgical operations. The study included 20 adult patients who received a surgical treatment because of degenerative spine changes. Measurements of the concentration of the VEGF-A in the patients' blood serum were taken three times (the first time--before the operation; the second time--during the first 24 hours after surgery; and the third time--between the fifth and the seventh day after the operation). No statistically significant correlation between the concentration of VEGF-A in the patients' blood serum before and after the operation was noted. A statistically significant correlation between the concentration of VEGF-A in the individual measurements was found. It can be concluded that people with a higher concentration of VEGF-A before surgery obtained a higher concentration of VEGF-A in the measurements taken after the operation. There is a statistically significant link between the patient's age and the concentration of VEGF-A during the immediate postoperative period (the older the patient, the higher the level of VEGF-A is observed).

Inhibitors of the blood coagulation process in patients with essential thrombocythemia.

: The aim of the study was to assess the activity of protein C, protein S and tissue factor pathway inhibitor in relation to the risk factors for thrombotic complications in patients with essential thrombocythemia.The study group consisted of 45 newly diagnosed patients with essential thrombocythemia. Protein S activity was determined by chromogenic method. Activities of protein C and tissue factor pathway inhibitor (TFPI) were determined using ELISAs.Significantly lower protein C and protein S activity but higher TFPI activity were found in patients with ET in comparison with the control group. TFPI activity was higher in women as compared to men, and in patients over 60 years of age compared with patients below 60 years of age. TFPI activity was higher in patients with leukocytes count at least 11 g/l than in patients with leukocytes count below 11 g/l and the difference almost reached statistical significance. Significantly lower protein C activity was found in patients with the JAK2V617F mutation, in comparison with essential thrombocythemia patients JAK2V617F (-).The reduced protein C and protein S activity may be one of the pathogenic factors of increased prothrombotic state in essential thrombocythemia patients. The decreased protein C activity in patients with the JAK2 V617F mutation seems to confirm the significant role of this mutation in the pathogenesis of thrombotic complications in essential thrombocythemia patients. Significantly increased TFPI activity in essential thrombocythemia patients above 60 years of age and with leukocyte count above 11 g/l expresses the activation of the compensatory mechanism for increased prothrombotic activity.

Ginsenoside contents in Panax quinquefolium organs from field cultivation.

Quantitative composition of saponins (ginsenosides) in Panax quinquefolium originating from field cultivation in Poland and harvested at the beginning of the growing season, during the blossoming period and at the end of growth was determined. A colourimetric method gave lower values compared to results of HPLC analysis, but the tendency of change in the content of saponins was similar in both instances. Ginsenoside amounts in P. quinquefolium organs changed depending on the specific time during the vegetation season the samples were taken. This study found that the highest content of these metabolites--66 mg/g d. w.-- occurred in the roots of the plant at the time of bloom. Two among the six metabolites examined in our study were dominant independently of the vegetation season. These were Rb1 and Re, with values of 25.4-33.8 mg/g d. w. and 16.4-19.7 mg/g d. w., respectively.

Selected Parameters of Angiogenesis and the JAK2, CALR, and MPL Mutations in Patients With Essential Thrombocythemia.

The aim of the study was to evaluate selected angiogenic factors in patients with essential thrombocythemia (ET) depending on JAK2V617F, calreticulin gene (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations. Sixty ET patients and 20 healthy volunteers were enrolled in the study. The following tests were performed: vascular endothelial growth factor- A (VEGF-A), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1),soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), platelet-derived growth factor( PDGF-BB), and stromal-derived factor-1α (SDF-1α). We observed an increased PDGF-BB level in patients with ET compared to the controls. Patients with CALR mutation had significantly higher concentration of PDGF-BB and lower concentration of SDF-1α than patients with JAK2V617F mutation. High concentration of PDGF-BB and low concentration of SDF-1α in patients with CALR(+) ET may indicate a contribution of these chemokines in disturbed Ca2+ metabolism in platelets.

Recombinant strains of Escherichia coli for L-aspartic acid biosynthesis.

The aspartase overproducing mutant B-715 was used as a donor of the aspartase gene for further construction of the aspartase-hyperproducing strains by molecular cloning. In preliminary experiments activity of transformants and their efficiency in L-aspartic acid biosynthesis were compared. The conditions for recombinant strain multiplication, biomass activation and L-aspartic acid biosynthesis were optimized. The optimum temperature for cells multiplication, their activation and for product biosynthesis was 37 degrees C. Two-stage process of the multiplication of bacteria (first in LB medium, and then in FF medium) eliminates the appearing of the inclusion bodies of aspartase in the cells. The shaking during cell activation improved cells productivity. The change of pH in the course of the biosynthesis process was insignificant but did not influence the process.

Selection and activation of Escherichia coli strains for L-aspartic acid biosynthesis.

The strain of Escherichia coli K-12 with high aspartase activity was irradiated with UV. After mutagenesis and selection, the mutant B-715 was isolated which was 4-times more active in L-aspartic acid biosynthesis than parental K-12 strain. The highest productivity was achieved while the strain was cultivated in the ammonium fumarate medium in 37 degrees C for 18-30 hours. It was found that better results were obtained when before the main production step of biosynthesis of L-aspartic acid, the cells of E. coli B-715 were incubated in the activation medium with ammonium fumarate. Activation at 37 degrees C was the most advisable for high efficiency of L-aspartic acid biosynthesis. The productivity of E. coli B-715 during 1 hour biosynthesis process was at the range 0.19-0.35 g of L-aspartic acid per 1 gram of dry mass (biomass) per minute.

[Haemostatic disturbances in essential thrombocythosis]. / Zaburzenia hemostazy w nadplytkowosci samoistnej.

Essential thrombocythemia (ET) is one of the chronic myeloproliferative disorders which is characterized by megakaryocytic metaplasia. The most common complications of ET are thrombohemorrhagic events. The overall incidence of thrombosis is 70% and hemorrhagic events about 10-15%. We investigated 21 patients with ET. Median age was 51.0 (range 41-61 years). 29 healthy controls were similar in aspects of sex and age. Patients had examined whole blood count, blood smear, platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), euglobulin lysis time (ELT), fibrin degradation products (FDP), thrombin-antithrombin III complexes (TAT), plasmin-alpha2-antiplasmin complexes (PAP), antigen of tissue and urokinase plasimogen activators (t-PA:Ag, u-PA:Ag), antigen of tissue plasminogen activator inhibitor types 1 and 2 (PAI-1:Ag, PAI-2:Ag), fibrinogen, antitrombin (AT) and alpha2-antiplasmin (alpha2-AP) activity. TAT concentraction (26.83 ng/ml) was significantly higher in ET group than in controls (3.41 ng/ml). We also showed in patients with ET significantly prolonged aPTT (50.12 s) and elevated platelet count (859.5 G/l). Fibrinolytic parameters PAI-1:Ag (56.2 ng/ml) and PAP (662.5 ng/ml) were significantly higher in patients with ET. High TAT concentration means enhanced thrombinogenesis and prolonged aPTT-disturbances in coagulation activation process. A cause of increased plasminogenesis is increased concentration of PAP.

[Hemostatic disturbances in chronic myeloid leukemia]. / Zaburzenia hemostazy w przewleklej bialaczce szpikowej.

UNLABELLED: Chronic myeloid leukemia (CML) is one of the chronic myeloproliferative disorders. Haemostatic disturbances and infections are the main causes of death in CML. MATERIAL AND METHODS: We investigated 22 patients with CML aged 38-55 years (median 45.0). Twenty nine healthy controls were sex and age-matched. Patients underwent following examination: whole blood count, blood smear, platelets count, prothrombin time (PT), activated partial thromboplastin time (aPTT), euglobulin lysis time (ELT), fibrin degradation products (FDP), thrombin-antithrombin complexes (TAT), plasmin-alpha2-antiplasmin complexes (PAP), antigen and urokinase plasminogen activators (t-PA:Ag, u-PA:Ag), antigen of tissue plasminogen activator inhibitors type 1 and 2 (PAI-1:Ag, PAI-2:Ag), fibrinogen concentrations, antitrombin (AT) and alpha2-antiplasmin (alpha2-AP) activity. RESULTS: TAT concentration (35.46 ng/ml) was significantly higher in examined group than in controls (3.41 ng/ml). Significantly higher fibrinogen concentration (3.31 g/l) and elevated platelet count (611.0 G/1) was observed in patients with CML. We also showed significantly higher concentrations of u-PA:Ag (0.67 ng/ml), PAI-1:Ag (34.8 ng/ml), PAP complexes (473.10 ng/ml) and FDP (17.10 microg/ml) in patients with CML. CONCLUSION: High TAT, fibrinogen concentrations and elevated platelet count in patients with CML are the evidences of an activation of coagulation. On the other hand fibrinolysis activation is proved by higher concentrations of u-PA:Ag, PAI-1:Ag, complexes PAP and FDP.

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in diabetic foot syndrome.

PURPOSE: The aim was to evaluate tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) concentration using enzyme linked immunosorbent assay method (ELISA) in diabetic foot syndrome (DFS) as compared to a group of healthy people and patients with diabetes mellitus without symptomatic vascular complications (DM2T). MATERIAL/METHODS: Venous blood samples were collected from 90 patients with type 2 diabetes mellitus (30 - DM2T; 60 - DFS). Age-matched controls were also included (n=30). tPA and PAI-1 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found a significantly lower concentration of tPA:Ag in patients with DFS in comparison to the DM2T group; tPA concentrations were significantly higher in DM2T as compared to the control group. We observed significantly lower concentration of PAI-1:Ag in DF patients treated for hypertension as compared to patients without hypertension. The tPA:Ag and PAI-1:Ag concentration analysis in DFS depending on age, gender and BMI did not show any significant differences. CONCLUSIONS: A lower concentration of tPA in patients with DFS may be associated with damage to the endothelial cells, especially in the microvasculature, and the sympathetic nervous system.

[Thrombinogenesis in chronic myeloproliferative syndromes]. / Trombinogeneza w przewleklych zespolach mieloproliferacyjnych.

UNLABELLED: Haemostatic disturbances are important in clinical complications in patients with chronic myeloproliferative syndromes and sometimes the reason of death. Pathogenesis of thrombo-embolic disease during these states is not clear. The aim of study was the evaluation of the risk of thrombosis in patients with chronic myeloproliferative syndromes using very detailed test to measure the concentration of TAT (thrombin-antithrombin) complexes. MATERIAL AND METHODS: The study was performed in 73 patients: in 22 with chronic myeloid leucaemia (CML), in 25 with polycythemia vera (PV), in 21 with essential thrombocytemia (ET) and in 5 with myelofibrosis (MF). The control group consisted of 29 healthy volunteers. In the blood plasma of studied persons concentration of TAT complexes and antithrombin (AT) activity were detected. RESULTS: We observed in patients, except MF, significant increase of TAT but diminished AT activity. CONCLUSIONS: Increased TAT complexes in chronic myeloproliferative syndromes is the evidence of significant thrombinogenesis. AT activity diminished in PV showes too high consumption of it with concomitant low synthesis.

Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery.

OBJECTIVES: The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. METHOD: Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. RESULTS: A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). CONCLUSION: High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions.

Activation of the tissue factor-dependent extrinsic pathway and its relation to JAK2 V617F mutation status in patients with essential thrombocythemia.

Thrombotic complications may occur in 7.6-29.4% of patients with essential thrombocythemia. According to the cellular theory, tissue factor (TF) activating extrinsic blood coagulation pathway is essential for the activation of blood clotting. The aim of the study was to evaluate the activation of the TF-dependent extrinsic pathway in patients with essential thrombocythemia, depending on the presence or absence of the Janus kinase 2 (JAK2) V617F mutation. The study included 74 newly diagnosed patients (F/M: 47/27; mean age 61 years) with essential thrombocythemia (Tefferi and Vardiman, Leukemia 2008; 22(1):14-22). Patients were diagnosed in the Department of Clinical Hematology and Hematological Malignancies University Hospital No. 2, Bydgoszcz, Poland. The control group consisted of 30 healthy volunteers (F/M: 17/13; mean age 49 years). The concentration and activity of TF and TF pathway inhibitor (TFPI) were measured using ELISA method. In patients with essential thrombocythemia, we observed a higher concentration of TF [median (Me) = 686.90 vs 164.28 pg/ml] and over 10-fold higher activity of TF (Me = 46.05 vs 4.01 pmol/l) when compared with the control group. We also reported significantly higher activity of TFPI compared with the control group (Me = 1.93 vs 1.78 U/ml). Moreover, a concentration of TFPI was significantly lower in patients with essential thrombocythemia with JAK2 V617F mutation as compared with patients without the mutation (Me = 1.90 vs 2.16 U/ml; P = 0.039639). Increased TF activity and concentration is responsible for higher procoagulant potential in patients with essential thrombocythemia. Reduced activity of TFPI in patients with essential thrombocythemia with JAK2 V617F mutation indicates an increased prothrombotic risk in this group of patients.

Extrinsic blood coagulation pathway and risk factors for thrombotic events in patients with essential thrombocythemia.

INTRODUCTION    The clinical course of essential thrombocythemia (ET) is varied, and some patients do not exhibit any clinical signs of the disease at the time of diagnosis. The most frequent complications that occur during the course of ET are hemostasis abnormalities manifesting as hemorrhagic or thrombotic events. The mechanism of thrombotic events in patients with ET is complex and not fully understood. OBJECTIVES    The aim of the study was to evaluate the concentration and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI), depending on the most important risk factors of thrombotic complications (age >60 years, history of thrombotic episodes, presence or absence of the JAK2 V617F mutation, and increased leukocyte count). PATIENTS AND METHODS    The study group included 113 patients with diagnosed ET, and the control group, 30 healthy volunteers matched for age and sex. The concentration and activity of TF and TFPI were measured using enzyme-linked immunosorbent assays. RESULTS    Patients with ET had a significantly higher activity and concentration of TF and increased activity of TFPI, as compared with controls. The analysis of the studied parameters in relation to risk factors revealed that patients with ET with a history of thrombotic events had a significantly higher concentration of TF, and patients with the JAK2 V617F mutation had a lower TFPI activity, as compared with patients without the mutation. CONCLUSIONS    Our study showed that in patients with ET who have a history of thrombosis or the JAK2 V617F mutation, the enhanced risk of thrombosis may result from an increased TF concentration or decreased TFPI activity.

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia.

OBJECTIVE: Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A (VEGF-A) and its soluble type-1 and type-2 receptors (sVEGFR-1 and sVEGFR-2) in plasma of patients with peripheral arterial disease (PAD) depending on the level of nutrition according to body mass index (BMI). METHODS: The study group included patients suffering from symptomatic PAD (n=46) in Fontaine classes IIa-IV without any history of neoplastic disease and who have a normal BMI (n=15), are overweight (n=21) or are obese (n=10). The control group (n=30) consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The group of patients with PAD co-existent with being overweight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMI. A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 (R=0.37, P=0.0103). However, no significant correlation was noticed between BMI and VEGF-A or sVEGFR-1 concentrations. CONCLUSIONS: A positive correlation determined between the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.

Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2.

OBJECTIVE: Uncontrolled diabetes has become a major cause of mortality and morbidity by reason of vascular angiopathy. The aim of this study was to evaluate the concentrations of soluble forms of vascular adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E-selectin, and thrombomodulin in patients with well-controlled and uncontrolled diabetes type 2. METHODS: The study was conducted on 62 patients with diabetes. Group I consisted of 35 patients with well-controlled diabetes. The second group included 27 patients with uncontrolled diabetes with micro-albuminuria. A control group was made up of 25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and soluble thrombomodulin were assayed in plasma. Serum concentration of creatinine was measured and the plasma concentrations of fasting glucose and glycated hemoglobin (HbA1c) determined. RESULTS: Lower concentrations of ICAM-1 were found in the group of uncontrolled diabetes patients compared with those with well-controlled disease. In patients with uncontrolled diabetes, VCAM-1 levels were significantly higher compared with the group with well-controlled diabetes. In patients with uncontrolled diabetes a positive correlation was obtained between glomerular filtration rate and sE-selectin and a negative correlation between the levels of creatinine and ICAM-1, although there was a positive correlation between (HbA1c) and ICAM-1. CONCLUSIONS: The study confirmed the participation of the inflammatory process associated with impaired vascular endothelial function in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and ICAM-1 in complications of diabetes.