Anna Thielemann

Endothelial dysfunction in patients with primary hypertension and hyperhomocysteinemia

It is widely accepted that endothelial dysfunction is the basis of the development of cardiovascular diseases, including hypertension. With regard to hypertension, endothelial dysfunction is concerned mainly with impaired vascular expansion; however, it is also related to the intensity of the development of atherosclerosis and thrombosis. Among the factors that cause damage to the endothelium, along with classic risk factors, is hyperhomocysteinemia. Hyperhomocysteinemia promotes the formation of oxygen radicals, lowering the oxidation-reduction potential, adversely affects the biosynthesis and function of vasodilator factors in the vascular wall, contributes to the inhibition of endothelial cell division with intense myocyte proliferation and migration, and impairs production of extracellular matrix components in the vascular wall. In addition, high levels of homocysteine and its derivatives contribute to the modification of LDL and HDL particles, inflammation and disorders in coagulation and fibrinolysis. Biochemical effects of the impact of hyperhomocysteinemia on endothelium can lead to damage of endothelial cells, dysfunction of diastolic function of vessels and reduction of their flexibility through its influence on vascular wall remodeling. These changes lead to an increase in blood pressure, strengthening the development of hypertension and target organ damage in patients with this disease.

Hyperhomocysteinemia, lipid and lipoprotein disturbances in patients with primary hypertension

PURPOSES The main aim of the study was to answer two questions: what are the concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I (apolipoprotein A-I), apo B (apolipoprotein B) and Lp(a) (lipoprotein(a)) in serum of patients with primary hypertension and with hyperhomocysteinemia? Is there any correlation between the concentration of homocysteine in blood serum and investigated lipid and lipoprotein parameters in patients with primary hypertension? MATERIAL/METHODS We investigated 42 patients with primary hypertension, aged 22-57. The control group consisted of 20 healthy volunteers. The concentration of homocysteine in serum was evaluated using immunochemical method (FPIA - Fluorescence Polarization Immunoassay). The concentration of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides in blood serum were estimated using enzymatic method. Apo A-I, apo B and lipoprotein(a) were assessed using nephelometric method. RESULTS The analysis of the results revealed statistically significant lower concentrations of HDL-cholesterol and apo A-I in blood serum of patients with primary hypertension and hyperhomocysteinemia than in the population with hypertension and normohomocysteinemia. Negative correlation between homocysteine and HDL-cholesterol as well as apo A-I has been revealed. CONCLUSION Quantitative analysis of the concentration of lipids and lipoproteins in blood serum in patients with primary hypertension and hyperhomocysteinemia may suggest that this type of human population might be more susceptible to atherosclerosis than those with primary hypertension and normal values of homocysteine.

The Determination of VEGF and MVD, among Patients with Primary Breast Cancer

The purpose of the study was to ascertain the value of assessment of vascular endothelial growth factor (VEGF) levels and microvessel density, and to search for correlations between them, in women with breast cancer. The assessment considered factors such as the stage of clinical disease advancement—according to International Union Against Cancer, the grade of histological malignancy, status of axillary lymph nodes and the size of the primary tumour. The concentration of VEGF was assessed in the plasma of 103 women with breast cancer, using an immunoenzymatic method (Quantikine test of R&D Systems). Assessment of microvessel density was performed using histopathological immunoperoxidase methods, using an anti-von Willebrand factor antibody (DAKO A/S). A statistically significant relationship was found between rising VEGF levels and microvessel density in women with breast cancer, when compared to values from a control group. A correlation was found between VEGF concentration and microvessel density (MVD) values. Statistically significant differences were found between VEGF levels of patients in stages I, II and III of clinical disease advancement. For MVD, differences were found only between stages I and III. A statistical relationship was also found between VEGF and MVD and tumour size. Similar results were found between VEGF concentrations in women with metastases to the axillary lymph nodes and cytokine levels in women with no metastases. The results of the study suggest that the degree of tumour vascularization and the concentration of VEGF may represent valuable indicators for the assessment of the angiogenic process in women with breast cancer.

The clinical usefulness of assessing the concentration of cell adhesion molecules sVCAM-1 and sICAM-1 in the serum of women with primary breast cancer.

Aim of the study Assessment of the concentrations of the soluble forms of the cell adhesion molecules sVCAM-1 and sICAM-1 in serum of female breast cancer patients. These concentrations were assessed in relation to factors such as: age, clinical stage of disease, histological grade of malignancy, the status of the local axillary lymph nodes, and the size of the primary tumour. Material and methods A total of 103 patients with primary breast cancer, aged 29 to 89 years, were investigated. The control group consisted of 40 healthy women. The concentration of sVCAM-1 and sICAM-1 was assessed using an enzyme-linked immunosorbent assay (ELISA). Results The results of the study suggest that the level of sVCAM-1 and sICAM-1 in the serum of women with breast cancer was significantly higher than that seen in the serum of healthy women. A relationship between the level of adhesion molecules and the stage of clinical disease advancement was discovered. There was a correlation between the increasing concentrations of sVCAM-1 and sICAM-1 and with the aggressiveness of the disease. Significant differences were also found in the group of women with metastases to the axillary lymph nodes and women with no metastasis. Similar correlations were found between sVCAM-1 and sICAM-1 levels and the size of primary tumour. Conclusions The results obtained suggest that the assessment of the soluble forms of sVCAM-1 and sICAM-1 may be useful indicators in the assessment of the clinical advancement of breast cancer.

Impact of administration of folic acid on selected indicators of inflammation in patients with primary arterial hypertension.

UNLABELLED The results of epidemiological and clinical tests have shown that in patients with primary arterial hypertension, a chronic mild inflammation develops. The purpose of the study was to determine whether administration of folic acid to patients with primary arterial hypertension influences concentrations of indicators of inflammation: hsCRP, sICAM-1 and sVCAM-1. MATERIAL AND METHODS The examination was carried out in 41 patients with primary arterial hypertension, aged 19-65 (21 men and 20 women), without complications of hypertension and/or coexisting diseases. The examined patients were administered 15 mg of folic acid once a day for 45 days. Before and after administration of folic acid, concentrations of folic acid, homocysteine, hsCRP, sICAM-1 and sVCAM-1 in serum were assessed. Concentrations of folic acid and homocysteine were determined using the immunoenzymatic method (Abbott) on an AxSYM analyzer. The level of C-reactive protein (CRP) was determined with an ultra-sensitive turbidimetric assay on a Dimension analyzer (Siemens). Next, concentrations of adhesion particles sICAM-1 and sVCAM-1 were assessed with the ELISA technique (R&D). RESULTS After the administration of folic acid in patients with primary arterial hypertension, a significant decrease in median concentrations of homocysteine in blood was observed. Simultaneously, the median hsCRP, ICAM-1 and VCAM-1 concentrations in serum in patients with primary arterial hypertension were significantly reduced. CONSLUSIONS Administration of folic acid to persons with primary arterial hypertension in a dose of 15 mg/ day for 45 days caused a decrease in the concentration of homocysteine in serum. That could indirectly result in the decrease in concentrations of the indicators of inflammation (hsCRP, ICAM-1 and VCAM-1), as it is apparent from previous studies that hyperhomocysteinemia stimulates the synthesis of CRP and the expression of adhesion molecules.

High concentration of urokinase-type plasminogen activator receptor in the serum of women with primary breast cancer.

Aim of the study The purpose of this study was to assess the concentration of urokinase-type plasminogen activator receptor (uPAR) in the serum of 103 women with breast cancer. Commonly recognized prognostic factors were taken into account, including age, histological grade of malignancy, stage of clinical advancement of the disease, status of local axillary lymph nodes and the size of the primary tumour. Material and methods The concentration of uPAR was assessed using an enzyme-linked immunosorbent assay (R&D Systems). Results The concentration of uPAR in women with breast cancer was found to be higher than in a control group and the difference was statistically significant. The concentration of uPAR was found to increase in line with increasing disease stage and this too was of statistical significance. Raised levels of uPAR were found in women with breast cancer both with and without metastases to the lymph nodes of the axilla. A positive relationship was also found between the concentration of the tested receptor and the size of the primary tumour. No significant relationship, however, was found between the concentration of uPAR and the histological grade of malignancy of the tumour. No statistically significant results were obtained regarding the menopausal status of the women, that is, whether they were pre- or post-menopausal. Conclusions Concentration of uPAR in serum of women with breast cancer is positively correlated with the stage of advancement of the disease. Thus, the assessment of this parameter can be useful in the clinical evaluation of women with breast cancer.

The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension

The aim of the study was the assessment of the impact of supplementation with folic acid on the concentration of homocysteine, total cholesterol (TC), HDL- and LDL-cholesterol, triglycerides (TG), apoprotein AI (apoAI) and apoprotein B (apoB) in patients suffering from primary hypertension. The examined group comprised 42 patients suffering from primary hypertension. All examined patients underwent laboratory tests as follows: concentration of homocysteine, folic acid, TC, LDL-cholesterol, HDL-cholesterol, TG, apoAI and apoB. All patients were orally administered with 15 mg of folic acid per day for 45 d. After this period, all laboratory tests were repeated. Homocysteine concentration was measured by the FPIA method, concentrations of apoAI and apoB were measured by the nephelometric method, and other parameters with routine methods. After administration of 15 mg of folic acid to patients with primary hypertension, a considerable decrease in the concentration of homocysteine was observed in parallel with a substantive growth of HDL-cholesterol, as well as apoprotein AI concentrations and a reduction of the apoprotein B concentration. Results of statistical analysis indicated a significant correlation between the decline in homocysteine concentration and the increase in HDL-cholesterol concentration, as well as between the increase of folic acid concentration and the increase in apoAI concentration in patients following the intake of folic acid. The drop in homocysteine concentration through the supplementation with folic acid can cause quantitative changes in the lipid and lipoprotein parameters which, in consequence, may lead to the mitigation of risk concerning the development of atherosclerosis.