Abstract. Cyclosporine belongs to the group of the most commonly used immunosuppressants. Hypertension occurs in approximately 30% of patients treated with this drug. However, the pathogenesis of this occurrence has not been explained to date. The purpose of our study was to clarify the mechanisms leading to the evolution of hypertension induced by cyclosporine A (CsA). We examined the changes in transmission within receptors and around the receptors. We also aimed to elucidate the mechanisms responsible for averting arterial hyperresponsiveness induced by the drug. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Tissues surrounding the artery were removed and the proximal segment (length of 2-3 cm) was used for cannulation. Cannulated arteries were placed in a 20-ml glass chamber (vertical position). The contraction force in our model was measured by an increased degree of perfusion pressure with a constant flow rate (approximately 1 ml/min). The results showed that in the presence of CsA, the concentration-response curves/phenylephrine (PHE) curve shifted to the left. Cyclosporine increased the reactivity of the arteries to PHE. This effect was directly linked to the increase in the receptor reserve. The analysis of the reactivity of vascular smooth muscle showed that CsA increased the influx of calcium ions from the extracellular to the intracellular area. No difference was found between the contraction triggered by Bay-K8644 in the presence of CsA and the control probe. The increase in perfusion pressure induced by CsA was blocked by L-type calcium channel blockers (nifidipine and diltiazem). The results from our experiments show that CsA increases the reactivity of vessels to the effect of catecholamines. CsA also enhances signal transmission between G-protein coupled receptors (GPCRs) and calcium channels. The activation of protein kinase C also plays a significant role in this process. Our results suggest that the best choice for the pharmacotherapy of hypertension induced by CsA would be calcium channel antagonists.

The aim of this study was to establish the criteria for methodology of cellular “anti-IGF-I” therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell “vaccines” should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8+and CD8+28+molecules and a switch from CD8+11b+to CD8+11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for “anti-IGF-I” strategy: characteristics sine qua non of injected “vaccines” (cloned cells IGF-I(−) and MHC-I(+)) and of PBL cells (CD8+increased level).

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Background. In patients with intracranial tumors, hypercoagulability is observed due to brain tissue and tumor cells being the source of tissue factor.

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.