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The aim of the study was to investigate the concentration and activity of tissue factor (TF) and Tissue factor pathway inhibitor (TFPI) as well as the concentration of thrombin-antithrombin (TAT) complexes in patients with primary and metastatic intracranial neoplasms. The study included 69 patients with an average age of 62 years. Twenty-one patients were diagnosed with gliomas, 18 meningioma stage II (M) patients, and 30 metastatic brain tumour cases (Meta). The control group consisted of 30 individuals with a mean age of 57 years. In the plasma of all the participants and in tumour tissue-derived homogenate, the concentrations and activities of TF, TFPI, the concentration of TAT complexes and the concentration of total protein were measured. The results were converted per 1 mg of protein. The concentration of TF was over 80 times higher in the tumour tissue-derived homogenate in respect to patients' plasma levels. Plasma TF activity in intracranial cancer patients was almost six times higher compared with noncancer counterparts, while in the tumour tissue-derived homogenate it was more than 14 times higher than in the intracranial cancer patients' plasma, whereas the concentration of TFPI in the tumour tissue-derived homogenate was significantly lower than in the patients' plasma. However, a significantly higher TFPI activity in the tumour tissue derived than in the patients' plasma was reported. The high concentration and activity of TF, along with the coexisting low concentration and activity of TFPI in the plasma of intracranial tumour patients, is associated with a higher prothrombotic risk in these patients.

Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase and marker of endothelial dysfunction, but the question remains as to whether asymmetric dimethylarginine is a marker of cardiovascular episodes or their independent risk factor. ADMA/DDAH (dimethylaminohydrolase) pathway regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis due to its impact on the NO formation. The aim of the study was to assess the concentrations of asymmetric dimethylarginine and the angiogenic potential in the blood of subjects with type 2 diabetes (T2DM, n = 33) and patients with prediabetes ( n = 32)—impaired fasting glycemia and/or impaired glucose tolerance (WHO criteria). The study found that both the prediabetes group and subjects with T2DM had significantly elevated concentrations of asymmetric dimethylarginine, significantly high levels of VEGF-A, low ratio of sVEGF-R1/VEGF-A, and sVEGF-R2/VEGF-A. This may suggest endothelial damage at early stages of carbohydrate metabolism dysfunction—before T2DM is diagnosed. Higher proangiogenic potential in prediabetes and T2DM patients than in healthy subjects, is not only the effect of an increase in VEGF-A levels, but also reduced inhibition of circulating receptors.

Background: Atherosclerosis is a systemic disease. Among patients with atherosclerosis, those suffering from peripheral arterial disease (PAD) represent a group of individuals with particularly high death risk, especially during the course of critical limb ischemia (CLI). In the pathogenesis of PAD/CLI complications, blood coagulation disorders play a significant role. The study aim was to examine the activation of the coagulation system depending on tissue factor (TF) in patients with CLI as compared with those with intermittent claudication (IC). Methods: Before initiating proper treatment (invasive or maintenance), blood samples were collected from 65 patients with CLI and 15 with IC to measure the following selected hemostasis parameters: concentrations and activation of tissue factor (TF Ag and TF Act) and tissue factor pathway inhibitor (TFPI Ag and TFPI Act), concentrations of thrombin&ndash, antithrombin complex (TAT Ag) and fibrinogen, platelet count (PLT), and concentrations of tissue-plasminogen activator (t-PA Ag), plasminogen activator inhibitor 1 (PAI-1), and D-dimer. The control group included 30 healthy volunteers (10 female/20 male). Results: The values of all analyzed parameters (except for lower TFPI Act) were significantly higher in the blood of PAD patients (with respect to PLT only in the CLI subgroup) in comparison with healthy subjects. The blood of patients with CLI as compared to the IC subgroup revealed much higher concentrations of TF Ag (p &lt, 0.001), with slightly decreased TF Act, significantly lower concentrations of TFPI Ag (p &lt, 0.001), slightly increased TFPI Act, and significantly higher levels of TAT Ag (p &lt, 0.001), fibrinogen (p = 0.026), and D-dimer (p &lt, 0.05). Conclusions: In patients with CLI, we can observe coagulation activation and a shifting balance toward prothrombotic processes. Furthermore, increased concentrations of D-dimer suggest a secondary activation of fibrinolysis and confirm the phenomenon as a prothrombotic condition with heightened fibrinolysis.

The quotient of concentrations concerning the key proangiogenic factor, that is, the vascular endothelial growth factor (VEGF-A) and the angiogenesis inhibitor, namely, its soluble receptors (sVEGFR-1 or sVEGFR-2), seems to reflect increased hypoxia and intensity of compensation angiogenesis. Therefore, it can be an ischemic and endothelial dysfunction marker reflected in intermittent claudication (IC) or critical limb ischemia (CLI) in patients with symptomatic peripheral arterial disease (PAD). The main objective of this study was to evaluate the levels of VEGF-A/sVEGFR-1 and VEGF-A/sVEGFR-2—presented using a novelty acronym VASCULAR-1 and VASCULAR-2—in patients with IC and CLI, as well as displayed in 4 classes of severity of PAD. VASCULAR-1 and VASCULAR-2 were calculated using the plasma of venous blood sampled from 80 patients with IC (n = 65) and CLI (n = 15) and the control group (n = 30). Patients with CLI were reported to have a slightly higher index of VASCULAR-1 and double VASCULAR-2 levels as compared to patients with IC ( P = nonsignificant), and these markers were significantly higher than controls ( P < .01 and P < .01, respectively). VASCULAR-2 levels were observed to have an increasing tendency in the subsequent degrees of PAD severity according to the Fontaine classification ( P = .02). In view of the need to consider the role of the proangiogenic and antiangiogenic factor in the assessment of the so-called “angiogenic potential,” VASCULAR-1 ratio and VASCULAR-2 ratio may be a new useful biomarker of limb ischemia in patients with IC and CLI. However, this requires further studies and evidence on a very large group of patients with PAD.

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.

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.

Competitive inhibition of endothelial nitric oxide synthase (eNOS) is the main biological effect of asymmetric dimethylarginine (ADMA), i.e. the methylated derivative of L-arginine. The resulting low level of NO is becoming one of the elements of pathogenesis of numerous cardiovascular disorders, mainly related to atherosclerosis, but also other metabolic diseases including type 2 diabetes. It appears that a high level of ADMA is not only a marker of pathological conditions such as chronic kidney failure, but also a significant factor which damages the endothelium. Despite multiple studies, the mechanisms of reducing the level of ADMA, which would allow to inhibit the progression of cardiovascular diseases and effective treatment, e.g. by means of L-arginine supplementation or medicines which are lowering ADMA levels, are still unclear. Perhaps, linking ADMA with the processes of new blood cell formation (angiogenesis) will allow us to explain these multifactor mechanisms.

Introduction: In patients with diabetic foot syndrome (DFS), an inadequate angiogenic response is observed. The aim of this study was to evaluate the concentrations of VEGF-A, PDGF-BB, sVEGF-R2 and sVEGF-R1 in patients with diabetes-complicated diabetic foot syndrome and analyse them using selected clinical data. Material and methods: Forty seven diabetic patients, 25 women mean age 63 and 20 men mean age 60.5, with diabetic foot syndrome (DFS) were enrolled in the experimental group. To evaluate angiogenesis factors depending on Wagner grade, the subjects were divided into three subgroups: I — patients with 0 Wagner grade (n = 14); II — patients with 1,2,3 Wagner grades (n = 15); and III — patients with 4,5 Wagner grades (n = 18). The control group consisted of 20 healthy volunteers. The material for research was blood. Results: Significantly higher levels of VEGF-A and PDGF-BB in the DFS cases compared to controls were observed (VEGF-A p = 0.000001; PDGF-BB p = 0.000051). Analysis of angiogenic parameters according to the stage of diabetic foot syndrome advancement showed higher VEGF-A level (I: p = 0.000867; II: p = 0.001827; III: p = 0.000024) and PDGF-BB (respectively p = 0.004113, p = 0.004224, p = 0.002480) in all the subgroups. Decreased sVEGF-R2 concentrations were observed in the I (p = 0.054) subgroup and the III (p = 0.03524) subgroup. In this study, a strong positive correlation between VEGF-A and PDGF-BB was observed (R = 0.66; p = 0.000001). Conclusions: Our study revealed that proangiogenic factor levels were increased in DFS. This is associated with lower limb ischaemia and hypoxic conditions. The stage of diabetic foot syndrome advancement influenced VEGF-A and PDGF-BB concentrations. (Endokrynol Pol 2014; 65 (4):306–312)

Objective To assess the concentration of adiponectin, soluble E-selectin, soluble thrombomodulin and tissue activator plasminogen antigen in postmenopausal women who received oral or transdermal hormone therapy. Design Case–control study. Setting Polish university hospitals. Population Seventy-six healthy postmenopausal women. Method Forty-six women who received oral (n = 26) or transdermal (n = 20) hormone therapy and a control group without such medication (n = 30), all aged 44–58 years. Main outcome measures Plasma concentrations of adiponectin, soluble E-selectin, soluble thrombomodulin and tissue activator plasminogen antigen by enzyme-linked immunosorbent assay. Results We found a significantly higher concentration of adiponectin in women on oral and transdermal therapy in comparison to the control group and a significantly lower concentration of soluble E-selectin in women who received oral hormone therapy vs. the control group. A significantly higher concentration of tissue activator plasminogen antigen was obtained in the group of women using transdermal menopausal hormone therapy compared with those receiving oral therapy and with the control group. Conclusions Reduced levels of soluble E-selectin in women using menopausal hormone therapy could lead to reduction in the intensity of expression of the adhesion factors on the surface of the vascular endothelium. Menopausal hormone therapy might have advantageous effects on vascular endothelial function through adiponectin. Transdermal therapy may have adverse effects associated with elevated tissue activator plasminogen antigen levels and thereby the higher risk of ischemic heart disease.

Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to a reduction in fibrinolytic activity.

Hepcidin is a small protein involved in iron metabolism that also exhibits antibacterial and antifungal activities. Since its discovery in 2000 hepcidin has been extensively studied in many research centers. Usage of natural and synthetic hepcidin inhibitors can be applied as a powerful therapeutic tool that targets multiple types of anemia. In addition the pro- tein itself has a potential to placate increased absorption of iron in patients with � -thalassemia. Previous studies have char- acterized mechanisms of hepcidin synthesis as well as its biological activity, however methods enabling estimation of its concentration in biological materials remain obscure. The physiological role of hepcidin in iron metabolism as well as methods of its determination in serum and urine samples are described in this paper. Furthermore, the possible role of hepcidin and its molecular antagonists in health improvement is considered.

Introduction Data about angiogenic factors in diabetic foot syndrome (DFS) are insufficient. Therefore, in the present study we focus on circulating endothelial progenitor cells (EPCs) and two major angiogenic factors: vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF-2) in patients with DFS. Materials and methods We included 75 subjects: 45 patients with type 2 diabetes and 30 controls. The study group was divided into 2 subgroups: 23 patients with diabetic foot and 22 patients without diabetic complications. The concentration of VEGF-A, soluble VEGF receptor 2 (sVEGF-R2) and FGF-2 were measured in plasma samples. The number of circulating EPCs was determined in peripheral venous blood. The number of endothelial progenitor cells was measured with FACSCalibur flow cytometer using monoclonal antibodies directed against antigens specific for EPCs. Results In our study we observed significant higher levels of VEGF-A and FGF-2 and lower sVEGF-R2 concentration in patients with T2DM compared to healthy subjects. The conducted analysis showed decreased levels of VEGF-A and elevated levels of FGF-2 in patients with DM complicated DFS compared to diabetic patients without DFS. Increased circulating EPCs number was reported in patients with DFS, and the difference was almost statistically significant. Conclusions The high concentration of VEGF-A and FGF-2, and a positive correlation between them indicate their participation in the process of angiogenesis in T2DM. Decreased sVEGF-R2 may result from inactivation of VEGF-A during complexes formation.

In patients with diabetic foot syndrome (DFS), an inadequate angiogenic response is observed. The aim of this study was to evaluate the concentrations of VEGF-A, PDGF-BB, sVEGF-R2 and sVEGF-R1 in patients with diabetes-complicated diabetic foot syndrome and analyse them using selected clinical data.Forty seven diabetic patients, 25 women mean age 63 and 20 men mean age 60.5, with diabetic foot syndrome (DFS) were enrolled in the experimental group. To evaluate angiogenesis factors depending on Wagner grade, the subjects were divided into three subgroups: I - patients with 0 Wagner grade (n = 14); II - patients with 1,2,3 Wagner grades (n = 15); and III - patients with 4,5 Wagner grades (n = 18). The control group consisted of 20 healthy volunteers. The material for research was blood.Significantly higher levels of VEGF-A and PDGF-BB in the DFS cases compared to controls were observed (VEGF-A p = 0.000001; PDGF-BB p = 0.000051). Analysis of angiogenic parameters according to the stage of diabetic foot syndrome advancement showed higher VEGF-A level (I: p = 0.000867; II: p = 0.001827; III: p = 0.000024) and PDGF-BB (respectively p = 0.004113, p = 0.004224, p = 0.002480) in all the subgroups. Decreased sVEGF-R2 concentrations were observed in the I (p = 0.054) subgroup and the III (p = 0.03524) subgroup. In this study, a strong positive correlation between VEGF-A and PDGF-BB was observed (R = 0.66; p = 0.000001).Our study revealed that proangiogenic factor levels were increased in DFS. This is associated with lower limb ischaemia and hypoxic conditions. The stage of diabetic foot syndrome advancement influenced VEGF-A and PDGF-BB concentrations.

In the late 20th century endothelial progenitor cells (EPCs) were discovered and identified as cells capable of differentiating into endothelial cells. Antigens characteristic of endothelial cells and hematopoietic cells are located on their surface. EPCs can proliferate, adhere, migrate and have the specific ability to form vascular structure, and they have a wide range of roles: They participate in maintaining hemostasis, and play an important part in the processes of vasculogenesis and angiogenesis. They are sources of angiogenic factors, especially vascular endothelial growth factor (VEGF). EPCs exist in bone marrow, from which they are recruited into circulation in response to specific stimuli. Tissue ischemia is thought to be the strongest inductor of EPC mobilization. Local ischemia accompanies many pathological states, including diabetic foot syndrome (DFS). Impaired angiogenesis--in which EPCs participate--is typical of DFS. An analysis of the available literature indicates that in diabetic patients the number of EPCs declines and their functioning is impaired. Endothelial progenitor cells are crucial to vasculogenesis and angiogenesis during ischemic neovascularization. The pathomechanisms underlying impaired angiogenesis in patients with DFS is complicated, but the discovery of EPCs has shed new light on the pathogenesis of many diseases, including diabetes foot syndrome.

Chronic inflammation is the common feature of inflammatory bowel disease. Adhesion molecules of immunoglobin super family play a key role in infiltration of leucocytes to place of inflammation.was to investigate the concentrations of slCAM-1, sVCAM-1 i sPECAM-1 in children and youth with Crohn's disease and ulcerative colitis.The soluble adhesion molecules were studied in the serum of 31 patients with Crohn's disease (CD) and 27 with ulcerative colitis (uc) and 20 healthy controls in age 6-18. Groups of Crohn's disease and ulcerative colitis patients were divided according to Hyams and Truelove-Witts' indexes of disease activity. Serum levels of sICAM-1, sVCAM-1 and sPECAM-1 were measured using an enzyme-linked immunosorbent assay kit of Bender MedSystem.There were no statistical significant differences in the levels of sICAM-1, sVCAM-1 and sPECAM-1 between the Crohn's disease patients and the control group. sICAM-1 level of the patients with ulcerative colitis was statistical significant higher then those of controls (391.28 +/- 134.95 ng/ml vs. 319.91 +/- 77.86 ng/ml, p = 0.022). There were no statistical significant differences in the levels of sVCAM-1 and sPECAM-1 between the patients with ulcerative colitis and the control group. There were no statistical significant differences in the levels of sICAM-1, sVCAM-1 and sPECAM-1 between patients with the active Crohn's disease and with remission and between patients with active ulcerative colitis disease and with remission.Determine of sICAM-1, sVCAM-1 and sPECAM-1 in patients with inflammatory bowel disease could not be helpful in estimation of inflammation activity.

Chronic inflammation is the common feature of inflammatory bowel disease. Infiltration of leucocytes is mediated by definite adhesion molecules expressed on the surface of activated leucocytes, platelets and endothelial cells.to investigate the clinical value of determining concentrations of sE-selectin and sL-selectin in children and youth with Crohn's disease and ulcerative colitis.soluble adhesion molecules were studied in the serum of 31 patients with Crohn's disease (CD) and 27 with ulcerative colitis (UC) and 20 healthy controls aged 6-18. Crohn's disease and ulcerative colitis patients were divided according to Hyams and Truelove-Witts' indeces of disease activity. Serum levels of sE-selectin and sL-selectin were measured using an enzyme-linked immunosorbent assay kit of Bender MedSystem.sE-selectin levels of the inflammatory bowel disease patients were higher then those of controls and sL-selectin levels of the IBD patients were lower than those of controls but without statistical significant differences. The sE-selectin levels of Crohn's disease patients with active disease were statistically significant higher then those with remission of the disease (29,17 + 25,65 ng/ml vs 50,74 + 20,00 ng/ml). There was no statistically significant difference in the levels of L-selectin between patients with active disease and those with remission. There were no statistically significant differences in the levels of sE-selectin and sL-selectin between patients with active ulcerative colitis disease and patients with remission.determination of sE-selectin in children with Crohn's disease is of significance in estimation of inflammation activity.

Vascular endothelial cells play an important role in haemostasis. Similar to hepatocytes they synthesise many substances taking part in blood clotting and fibrinolysis.The aim of the study was the evaluation of markers of endothelial cells: von Willebrand factor (vWf) and thrombomodulin (TM) in children with chronic viral hepatitis.VWf and TM levels were measured using ELISA method. The examined group consists of 105 children with chronic viral hepatitis aged 2 to 18 years.The concentrations of vWf and TM were significantly higher in chronic viral hepatitis compared to controls. The values of TM were higher in chronic viral hepatitis B in comparison to hepatitis C and higher in boys than in girls. The markers of endothelial cells do not depend on the degree of inflammation and fibrosis.Increased levels of vWf and TM suggest stimulation of endothelial cells in children with chronic viral hepatitis B and C.

Disturbances of lipids metabolism described in obese persons are important factor damaging vascular endothelium. Known markers of endothelium impairment are: von Willebrand factor (vWf), tissue plasminogen activator (t-PA:Ag) and thrombomodulin (TM). The aim of the work was to evaluate markers of the endothelial disturbance in the blood plasma of persons with obesity. The study was performed in the group of 50 obese persons (39 W, 11 M) aged 35-65 (means 48.8) years with abdominal obesity. The control group consisted of 30 healthy volunteers aged 25-56 (means 41.0) years. In the poor platelet plasma obtained from venous citric blood concentrations of TM, von Willebrand factor antigen (vWf:Ag) and tissue plasminogen activator antigen (t-PA:Ag) were determined using immunoenzyme-linked assay (ELISA). In the obese persons significantly higher concentration of vWf:Ag and t-PA:Ag in comparison to control group. Analysis of results obtained according sex showed that in the blood plasma of obese women TM concentration was significantly higher than in healthy women. Our study proved that in the blood plasma of obese men there are evidences of impairment of endothelial function as higher concentration of vWf:Ag and t-PA:Ag, but in the group of obese women as the increased TM concentration.

Abnormalities of blood coagulation are a major part of acute and chronic viral hepatitis. In this study antithrombin III, protein C and protein S were determined in 100 children with chronic hepatitis B or C infection (range age 3-17) according to degree of hepatic histological activity and fibrosis. There was no statistically significant correlation between levels of examined parameters in children with chronic viral hepatitis compared with those in control group and between the degree of hepatic histological activity and fibrosis and coagulation parameters.