Tissue factor-dependent coagulation activation in intracranial neoplasms: a comparative study.

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.

The effects of humic water on endothelial cells under hyperglycemic conditions: inflammation-associated parameters.

Humic waters (HW) are globally unique, deep underground, dark-brown waters containing humic acids, and they present numerous therapeutic activities including anti-inflammatory. In the present study, we use HW from source in Poland. Diabetes has become an epidemic and is a risk factor of cardiovascular diseases. Hyperglycemia in diabetes is responsible for damaging of the endothelium and increases inflammation on the surface of the vascular lining. The inflammatory process in diabetes is associated with the secretion of inflammatory cytokines by endothelial cells, e.g., tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), and with the reduction of cell proliferation. In the study, we used cultures of endothelial cells (HUVEC line-human umbilical vein endothelial cells) with the addition 30 mM/L of glucose in the culture medium which imitated the conditions of uncontrolled diabetes. The addition of HW in the proper volume to the culture medium causes reduction of inflammation by significant decrease in inflammatory cytokines such as TNFα and IL-6 and also leads to enhancement of the cell proliferation. It appears that the adverse effects of hyperglycemia on vascular endothelial cells may be corrected by addition of humic water. The above promising results of in vitro tests provide an opportunity to the possible use of humic water in the supportive treatment of endothelial dysfunction disorders in diabetes. However, this issue requires further clinical research.

Low-level laser irradiation modifies the effect of hyperglycemia on adhesion molecule levels.

Endothelium plays a key role in maintaining vascular homeostasis by secreting active factors involved in many biological processes such as hemostasis, angiogenesis, and inflammation. Hyperglycemia in diabetic patients causes dysfunction of endothelial cells. Soluble fractions of adhesion molecules like sE-selectin and vascular cell adhesion molecule (sVCAM) are considered as markers of endothelial damage. The low-level laser therapy (LLLT) effectively supports the conventional treatment of vascular complications in diabetes, for example hard-to-heal wounds in patients with diabetic foot syndrome. The aim of our study was to evaluate the effect of low-energy laser at the wavelength of 635 nm (visible light) and 830 nm (infrared) on the concentration of adhesion molecules: sE-selectin and sVCAM in the supernatant of endothelial cell culture of HUVEC line. Cells were cultured under high-glucose conditions of 30 mM/L. We have found an increase in sE-selectin and sVCAM levels in the supernatant of cells cultured under hyperglycemic conditions. This fact confirms detrimental influence of hyperglycemia on vascular endothelial cell cultures. LLLT can modulate the inflammation process. It leads to a decrease in sE-selectin and sVCAM concentration in the supernatant and an increase in the number of endothelial cells cultured under hyperglycemic conditions. The influence of LLLT is greater at the wavelength of 830 nm.

A preliminary estimation of tissue factor pathway inhibitor (TFPI) and protein C in patients with intracranial tumors.

BACKGROUND: In patients with intracranial tumors, hypercoagulability is observed due to brain tissue and tumor cells being the source of tissue factor. OBJECTIVES: The aim of the study was to assess tissue factor (TF), tissue factor pathway inhibitor (TFPI) and protein C in the plasma and tumor tissue homogenate in patients with intracranial tumors. MATERIAL AND METHODS: The study included 77 patients; 24 patients were diagnosed with glioma, 20 patients with meningioma and 33 patients with metastatic tumors; mean age - 54 years. The material for the study was the plasma and tumor tissue homogenate sampled during surgery. The control group consisted of 30 controls; mean age - 51 years. In the plasma of all the participants and in tumor tissue homogenate, the concentrations of TF-Ag, TFPI-Ag and protein C activity, and the concentration of total protein were measured. The results were converted per mg of protein. RESULTS: In patients with intracranial tumors, elevated concentrations of TF-Ag, TFPI-Ag and protein C activity were noted, also after the conversion per mg of protein. A 100-fold higher concentration of TF per 1 mg of protein was found in tumor tissue compared to the patients' plasma. In tumor tissue homogenate, a lower TFPI concentration and a lower protein C activity were recorded. CONCLUSIONS: The study confirmed the essential prothrombotic properties in patients with intracranial tumors, expressed with an elevated TF level, as well as a tremendous amount of TF in tumor tissue homogenate derived from tumors. The elevated concentration of TFPI and protein C activity converted per mg of total protein should be analyzed in terms of their pleiotropic function, along with the participation in hemostasis control. It seems that the reduced protein C activity and low TFPI level are associated with the enormous TF value in tumor tissue homogenates.

Effect of a 3-Week Low-Calorie Diet and Balneological Treatment on Selected Coagulation Parameters in Morbidly Obese Patients.

BACKGROUND: The most common cause of death among people with obesity are cardiovascular complications as a result of a hypercoagulability state. OBJECTIVES: The purpose of the study was to assess the potential of coagulation system activation depending on the tissue factor and to analyze of the influence of a 3-week low-calorie diet and balneological treatment on selected coagulation parameters in morbidly obese patients. MATERIAL AND METHODS: The study included 36 patients (28 females and 8 males; mean age 46) with the value of BMI > 40 kg/m2. The study was designed in two stages: baseline and after 21-days. The evaluation of tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), fibrinogen, D-dimer, thrombin-antithrombin complexes (TAT), and the activity of antithrombin (AT) was performed in patients before and after the treatment. The control group consisted of 24 healthy volunteers (16 females and 8 males) at a mean age of 39 with BMI . 24.9 kg/m2. RESULTS: There were significantly higher levels of TF, TFPI, fibrinogen, TAT complexes and D-dimer in the study group as compared to the controls. Moreover, there were no significant changes in the parameters studied before and after the treatment. In the group of obese patients, there were significant positive correlations between the concentrations of vWF and BMI and BMI changes and a significant negative correlation between the WHR changes and TFPI concentration. CONCLUSIONS: The study confirmed that morbidly obese patients represent a high risk of hypercoagulability state, despite no clinical evidence, which could be due to the great inhibitory potential of TFPI in suppressing the extrinsic pathway of the coagulation system. However, the lack of effect of the 3-week exposure to the LCD and balneological treatment in morbidly obese subjects indicates that substantial fat mass must be reduced before adequate hemostasis is re-established.

Low-level laser irradiation effect on endothelial cells under conditions of hyperglycemia.

Diabetes mellitus is considered to be a very serious lifestyle disease leading to cardiovascular complications and impaired wound healing observed in the diabetic foot syndrome. Chronic hyperglycemia is the source of the endothelial activation. The inflammatory process in diabetes is associated with the secretion of inflammatory cytokines by endothelial cells, e.g., tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). The method of phototherapy using laser beam of low power (LLLT-low-level laser therapy) effectively supports the conventional treatment of diabetic vascular complications such as diabetic foot syndrome. The aim of our study was to evaluate the effect of low-power laser irradiation at two wavelengths (635 and 830 nm) on the secretion of inflammatory factors (TNF-α and IL-6) by the endothelial cell culture-HUVEC line (human umbilical vein endothelial cell)-under conditions of hyperglycemia. It is considered that adverse effects of hyperglycemia on vascular endothelial cells may be corrected by the action of LLLT, especially with the wavelength of 830 nm. It leads to the reduction of TNF-α concentration in the supernatant and enhancement of cell proliferation. Endothelial cells play an important role in the pathogenesis of diabetes; however, a small number of studies evaluate an impact of LLLT on these cells under conditions of hyperglycemia. Further work on this subject is warranted.

Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2.

OBJECTIVE: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. METHODS: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. RESULTS: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. CONCLUSIONS: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca(2+). The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications.

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.

Associations between selected angiographic parameters and the number of CD34⁺ cells and plasma levels of vascular endothelial growth factor and angiogenin in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: Left ventricular (LV) function and prognosis in patients after myocardial infarction are associated with some angiographic parameters. OBJECTIVES: The aim of the study was to assess the associations between the TIMI score in the infarct-related artery (IRA) before percutaneous coronary intervention (PCI), myocardial blush grade (MBG) following effective PCI, and the extent of collaterals measured using the Rentrop scale and plasma levels of vascular endothelial growth factor (VEGF) and angiogenin, number of CD34⁺ cells, as well as LV ejection fraction (LVEF) and wall motion score index (WMSI). PATIENTS AND METHODS: In 62 patients with the first ST-segment elevation myocardial infarction (STEMI) treated with PCI and bare metal stent implantation, plasma VEGF and angiogenin levels as well as the number of CD34⁺ cells were assessed before PCI, 24 hours after PCI, at discharge, and at 30 days following STEMI. LVEF and WMSI were evaluated by echocardiography at discharge and at 1 and 6 months after STEMI. RESULTS: Patients with TIMI 0-1 flow in the IRA before PCI (64.6% of the patients) had significantly higher troponin I and VEGF levels as well as a higher number of CD34⁺ cells than patients with TIMI 3 flow. Patients with TIMI 0-1 flow also had worse LV systolic function at 1 and 6 months following STEMI. Neither the MBG grade nor the Rentrop score showed associations with the mobilization of CD34⁺ cells, VEGF and angiogenin levels, and parameters of L V systolic function. CONCLUSIONS: Early patency of the IRA and lower myocardial necrosis seem to be more important for LV function assessed in patients 6 months after STEMI than mobilization of CD34⁺ cells and levels of angiogenic factors.

Effect of LLLT on endothelial cells culture.

Growth factors as vascular endothelial growth factor (VEGF), produced by the endothelial cells, take an essential part in pathological and physiological angiogenesis. The possibility of angiogenesis modulation by application of laser radiation may contribute to the improvement of its use in this process. Thus, the aim of the study was to investigate the influence of low-level laser therapy (LLLT) on the proliferation of endothelial cells, secretion of VEGF-A and presence of soluble VEGF receptors (sVEGFR-1 and sVEGFR-2) in the medium after in vitro culture. Isolated human umbilical vein endothelial cells (HUVECs) were irradiated using a diode laser at a wavelength of 635 nm and power density of 1,875 mW/cm(2). Depending on radiation energy density, the experiment was conducted in four groups: I 0 J/cm(2) (control group), II 2 J/cm(2), III 4 J/cm(2), and IV 8 J/cm(2). The use of laser radiation wavelength of 635 nm, was associated with a statistically significant increase in proliferation of endothelial cells (p = 0.0041). Moreover, at 635-nm wavelength, all doses of radiation significantly reduced the concentration of sVEGFR-1 (p = 0.0197).

A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus.

OBJECTIVE: Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A (VEGF-A) and its receptors in patients with well-controlled diabetes. METHODS: The study was conducted on 31 patients with well-controlled type 2 diabetes without micro- or macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin (HbA1c) was determined. RESULTS: No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein (HDL)-cholesterol in the study group. CONCLUSIONS: The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.

Insulin resistance as estimated by the homeostatic method at diagnosis of gestational diabetes: estimation of disease severity and therapeutic needs in a population-based study.

BACKGROUND: Chronic insulin resistance, exacerbated in the course of pregnancy, is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). We hypothesise that the degree of insulin resistance, assessed at diagnosis of GDM, is a parameter of its pathophysiologic heterogeneity and/or severity. Thus, it offers potential to open new avenues for the personalization of therapy in affected women. METHODS: 1254 Polish Caucasian women with GDM were recruited into the study. The following parameters were assessed in the course of the study: body mass index (BMI), parity, weight gain during pregnancy, glycated haemoglobin, glucose level during an oral glucose tolerance test (OGTT), insulin, insulin resistance and insulin secretion. The severity of GDM was assessed based on insulin use and daily insulin dose during gestation. In order to evaluate insulin secretion and insulin resistance the homeostatic method was used (HOMA-B and HOMA-IR, respectively). We compared all the metabolic parameters and methods of treatment of GDM in women subdivided by quartiles of insulin resistance. RESULTS: The HOMA-IR in the whole population ranged from 0.34 to 20.39. The BMI, fasting insulin, fasting glucose and insulin dose per day increased along with increasing quartiles (HOMA-IR > 1.29). We observed a decrease of HOMA-B in the third quartile (1.92-2.89) compared with the first quartile (0.34-1.29). Insulin treatment was associated with HOMA-IR (<1.29 vs. >2.89), OR: 3.37, fasting glucose (≤6.11 vs. >6.11 mmol/dl), OR: 2.61, age (≤30 vs. >30 y. o.), OR: 1.54, and BMI (<25 vs. ≥25 kg/m2), OR: 1.45. Maximum insulin dose was associated with HOMA-IR, OR: 2.00, after adjustment for family history of diabetes, and 2-h OGTT glucose. CONCLUSION: Insulin resistance assessed by the HOMA index at diagnosis is associated with the severity and pathophysiological heterogeneity of GDM. A HOMA-IR >1.29 points to the major role of insulin resistance, indicating the need for a treatment aimed at improving tissue sensitivity to insulin. A HOMA-IR 1.29-2.89 suggests reduced insulin secretion, which is an indication for the introduction of insulin therapy. A HOMA-IR >2.89 indicates insufficient compensation for insulin resistance, which suggests the need for a treatment aimed at improving susceptibility of tissues to insulin combined with insulin therapy.

Does mobilisation of CD34+ stem cells along with VEGF, angiogenin, IL-6, IL-8, and hsCRP levels allow predicting the direction of left ventricular ejection fraction and wall motion score index changes in patients with myocardial infarction?

BACKGROUND: Left ventricular (LV) systolic function is a significant prognostic factor in patients after myocardial infarction (MI). Multiple angiogenic and inflammatory factors are involved in postinfarction LV remodelling process. In addition, CD34+progenitor cells mobilised from bone marrow and tissue niches participate in regeneration of the infarcted myocardium. AIM: To examine relationships between LV ejection fraction (LVEF) and wall motion score index (WMSI) and the number of CD34+ cells and plasma levels of vascular endothelial growth factor (VEGF), angiogenin and such inflammatory factors as interleukin 6 (IL-6), interleukin 8 (IL-8), and high-sensitivity C-reactive protein (hsCRP) in patients with ST-elevation MI (STEMI). METHODS: The study group included 61 patients with STEMI treated with primary percutaneous coronary intervention (PCI)involving bare metal stent implantation. Plasma levels of the evaluated angiogenic and inflammatory factors were measured by flow cytometry at 4 time points (just before PCI, 24 h later, at hospital discharge, and 30 days after STEMI). LVEF and WMSI were measured by echocardiography at hospital discharge, 1 month later, and 6 months later. We compared angiogenic and inflammatory factor levels in patients with no improvement of the LV systolic function during the follow-up (group 1, n = 22)vs. those with improved LV systolic function (group 2, n = 39). RESULTS: No differences in the levels of VEGF, angiogenin, IL-6, IL-8, and hsCRP, and the number of CD34+ cells were observed between the two groups. Despite this, we found significant negative correlations between hsCRP level and LVEF,and positive correlations between hsCRP level and WMSI in both patient groups, but these correlations were much stronger in group 1. We also found a significant negative correlation between WMSI at 6 months and the number of CD34+ cells measured 24 h after PCI. CONCLUSIONS: 1. Evaluation of plasma VEGF, angiogenin, IL-6, IL-8, and hsCRP levels and the number of CD34+ cells at different time points in patients with STEMI did not allow predicting the direction of changes in LVEF and WMSI. 2. Observed significant correlations between hsCRP level and LVEF and WMSI may suggest a harmful effect of inflammation on postinfarction myocardial remodelling. 3. A significant negative correlation between the number of CD34+ and WMSI suggests that increased mobilisation of these cells might have a beneficial effect on systolic function after MI.

Adiponectin and endothelial markers in postmenopausal women taking oral or transdermal hormone therapy.

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.

PAI-1 and α2-AP in patients with morbid obesity.

BACKGROUND: Obesity is a multifactorial, progressing and life-long illness that consists in an exaggerated collection of fatty tissue. In 1997 WHO acknowledged that overweight and obesity had the character of an epidemic in developed countries. Studies show that in Poland morbid obesity was diagnosed in 2.2% of women and in 0.6% of men. Thromboembolic incidents occur very often in people with obesity, especially with morbid obesity. In hypercoagulability, fibrinolysis process decides about the scale of clinical symptoms of disorders of the hemostasis. OBJECTIVES: The aim of this study was to assess the chosen parameters of the fibrinolysis process in patients with BMI crossing 40, classified for surgical treatment of obesity. MATERIAL AND METHODS: The study was conducted in 50 patients with BMI > 40, including 30 women and 20 men. The mean age of the patients was 38.5 years. The control group was made up of 20 healthy volunteers, with a mean age of 38 years. In the blood of both groups the following examinations were performed: concentration of tissue plasminogen activator antigen (t-PA:Ag), antigen of the plasminogen activator inhibitor type-1 (PAI-1:Ag), D-dimers, fibrinogen and plasminogen, activity of the α2-antiplasmin (α2-AP). RESULTS: The conducted study showed that in patients with morbid obesity there was a higher concentration of tPA:Ag, PAI-1:Ag, D-dimers and a higher activity of α2-AP. CONCLUSIONS: The conducted study demonstrates that the activation of the fibrinolysis process appeared after the coagulation process, indicated by an increase in the t-PA:Ag concentration and D-dimers concentration in patients with morbid obesity. The essential growth of PAI-1:Ag level and α2-AP level shows strong inhibition of fibrinolysis in patients.

Elevation of sE-Selectin Levels 2-24 Months following Gestational Diabetes Is Associated with Early Cardiometabolic Risk in Nondiabetic Women.

Objective. We hypothesised that the endothelial dysfunction is associated with early glucose dysregulation and/or atherosclerosis risk factors in nondiabetic women with a previous history of gestational diabetes (pGDM). Material/Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA), lipids, biomarkers of endothelial dysfunction, and inflammation were evaluated in 85 women with pGDM and in 40 controls 2-24 months postpartum. Results. The pGDM group consisted of 67% normoglycemic women (pGDM-N) and 33% with prediabetic state (pGDM-P). The BMI, waist circumference, fasting and 2 h glucose (OGTT), soluble adhesion molecules, tissue plasminogen activator antigen, high sensitivity C-reactive protein, total-, LDL-cholesterol, and triglycerides/HDL-cholesterol ratio were higher in the pGDM women compared with the controls. After adjustment for BMI and fasting glucose, only higher triglycerides, higher TG/HDL and lower HDL-cholesterol were associated with pGDM. The pGDM-P differed from pGDM-N for only higher triglycerides and TG/HDL. The plasma level of sE-selectin was not independently associated with glucose concentration in pGDM group. sE-selectin level correlated with triglycerides, TG/HDL, plasminogen activator inhibitor-1 antigen, and sICAM-1. Conclusions. sE-selectin level correlated with components of metabolic syndrome, but only the atherogenic lipid profile was independently associated with a previous history of GDM in nondiabetic women 2-24 months postpartum.

Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

OBJECTIVE: To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. DESIGN: Prospective postpregnancy cohort study. SETTING: Polish university hospitals. SAMPLE: Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. METHODS: All women were studied 2-24 months (mean 12 ± 10 months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. MAIN OUTCOME MEASURES: We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels. RESULTS: Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83 mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high-sensitivity C-reactive protein and triglyceride/high-density lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E-selectin was independently associated with triglyceride levels. CONCLUSIONS: Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2-24 months after an index pregnancy. Normalization of triglycerides should be included in preventive therapy after a pregnancy complicated by gestational diabetes.

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy.

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.

Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A. MATERIAL/METHODS: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization. RESULTS: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent. CONCLUSIONS: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy.

Impaired fasting glucose as a marker of heterogeneity of gestational diabetes mellitus. A study of 1025 women living in the region of Kuyavia and Pomerania in Poland.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a heterogeneous disease. We hypothesized that fasting hyperglycaemia, defined as impaired fasting glycaemia (IFG), is a marker of metabolic heterogeneity of GDM. The aim of this study was to compare selected metabolic parameters in two groups of women with GDM, one with normal fasting glycaemia (NFG GDM) and another with IFG, to test this hypothesis. MATERIAL AND METHODS: Metabolic parameters of 1025 women with GDM (mean age 29 years): glucose and insulin at 0 OGTT, glucose at 2-h oral glucose tolerance test (OGTT), body mass index before pregnancy, parity, and gestational age at diagnosis of GDM were analyzed. Insulin resistance and beta-cell function were evaluated by HOMA indexes (HOMA-IR and HOMA-B) at the diagnosis of GDM. RESULTS: The IFG GDM group (23%) consisted of isolated IFG (30%), IFG/IGT (60%), and IFG/DM (10%). The NFG GDM group (77%) consisted of isolated IGT (98%) and NFG/DM (2%). Women with IFG GDM were characterized by higher prepregnancy BMI, earlier diagnosis of GDM, higher HOMA-IR (p < 0.03), and lower HOMA-B (p < 0.01) compared to NFG GDM. In the IFGGDM group, DM was characterized by lower HOMA-B compared with isolated IFG and IFG/IGT. In the NFG GDM group, isolated IGT and DM were characterized by similar HOMA-IR and HOMA-B. CONCLUSIONS: Impaired fasting glucose distinguishes more severe metabolic phenotypes of GDM compared toGDM with normal fasting glucose concentrations.