Rheological, haemostatic, endothelial and platelet abnormalities appear to play a role in the thrombotic complications of hypertension. This prothrombotic/hypercoagulable state in hypertension may contribute to the increased risk and severity of target organ damage. It can be induced by the activated reninangiotensin system (RAS), with abnormalities in endothelial and platelet function, coagulation and fibrinolysis. Treatment of uncomplicated essential hypertension by RAS targeting antihypertensive therapy could result in a reversal of prothrombotic abnormalities, contributing to a reduction of thrombosis-related complications. Since angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have two distinct mechanisms of RAS interruption, it is hypothesized that each therapy might have different impact on the prothrombotic state in hypertensive patients. Some studies demonstrate a beneficial effect of both ACE inhibitors and ARBs on prothrombotic state, in addition to their efficacy to normalize elevated blood pressure. The potentially antithrombotic effect of the RAS inhibiting agents may in turn support the preservation of cardiovascular function. Available data may offer an additional explanation for the efficacy of the RAS targeting agents in the prevention of cardiovascular events in patients with atherosclerotic vascular disease., A. Remková, M. Remko., and Obsahuje bibliografii a bibliografické odkazy
This review summarizes recent trends in the construction of bioartificial vascular replacements, i.e. hybrid grafts containing synthetic polymeric scaffolds and cells. In these advanced replacements, vascular smooth muscle cells (VSMC) should be considered as a physiological component, although it is known that activation of the migration and proliferation of VSMC plays an important role in the onset and development of vascular diseases, and also in re stenosis of currently used vascular grafts. Therefore, in novel bioartificial vascular grafts, VSMCs should be kept in quiescent mature contractile phenotype. This can be achieved by (1) appropriate physical and chemical properties of the material, such as its chemical composition, polarity, wettability, surface roughness and topography, electrical charge and conductivity, functionalization with biomolecules and mechanical properties, (2) appropriate cell culture conditions, such as composition of cell culture media and dynamic load, namely cyclic strain, and (3) the presence of a confluent, mature, semipermeable, non-thrombogenic and non-immunogenic endothelial cell (EC) barrier, covering the luminal surface of the graft and separating the VSMCs from the blood. Both VSMCs and ECs can also be differentiated from stem and progenitor cells of various sources. In the case of degradable scaffolds, the material will gradually be removed by the cells and will be replaced by their own new extracellular matrix. Thus, the material component in advanced blood vessel substitute s acts as a temporary scaffold that promotes regeneration of the damaged vascular tissue., M. Pařízek, K. Novotná, L. Bačáková., and Obsahuje bibliografii a bibliografické odkazy
Transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel activated by capsaicin, a pungent substance from chili peppers. It is considered to act as an integrator of various physical and chemical nociceptive stimuli, as it can be gated by noxious heat (>43ºC), low pH (protons) and also by recently described endogenous lipids. The structure and function of TRPV1 receptors was vigorously studied, especially since its cloning in 1997. However, most of the research was pointed towards the role of TRPV1 receptors in the peripheral tissues. Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission. The aim of this short review was to summarize the knowledge about TRPV1 receptors in the spinal cord dorsal horn, preferentially from morphological and electrophysiological studies on spinal cord slices and from in vivo experiments., D. Špicarová, J. Paleček., and Obsahuje bibliografii a bibliografické odkazy
The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of “cell-based coagulation model” which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs., M. A. Malý, P. Tomašov, P. Hájek, P. Blaško, I. Hrachovinová, P. Salaj, J. Veselka., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to explore changes in plasma vascular endothelial growth factor (VEGF) in aged patients who undergone transcatheter aortic valve implantation or balloon angioplasty for the treatment of aortic stenosis. Plasma VEGF was measured in subjects with diabetes mellitus type 2 (DM) (n=21, age 79.2±1.6 years) and in non-diabetic subjects (non-DM) (n=23, age 84.4±0.7 years), using an ELISA kit. Before the procedure plasma levels of VEGF were significantly lower in DM than in non-DM patients (P<0.05). Plasma VEGF significantly increased in both groups (DM and non-DM) 24 h (387±64 vs. 440±30 pg/ml, P<0.05) and 72 h (323±69 vs. 489±47 pg/ml, P<0.05) after the endovascular procedure. However, the VEGF in DM patients was significantly lower compared to non-DM subjects up to one month after the endovascular procedure (283±47 vs. 386±38 pg/ml, P<0.05). We conclude that increased plasma VEGF in aged patients associates with atherosclerotic aortic valve stenosis. In spite of that plasma VEGF in DM was constantly significantly lower than in non diabetic patients, both before and after the endovascular procedure, possibly reflecting a disturbance of angiogenic/antiangiogenic balance in diabetes., V. Bláha, J. Šťásek, J. Bis, J. Fortunato, C. Andrýs, V. Pavlík, P. Polanský, M. Brtko, L. Sobotka., and Obsahuje bibliografii
a1_Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients’ blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression., a2_ We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease., Simona Valášková, Andrea Gažová, Petra Vrbová, Tomáš Koller, Barbara Šalingova, Adriana Adamičková, Nikola Chomaničová, Nikoleta Hulajová, Juraj Payer, Ján Kyselovič., and Obsahuje bibliografii
The relationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf) in hypertensives with stroke in comparison with a group of stroke-free patients was evaluated. Twenty-six patients (aged 66±10 years, 11 females/ 15 males) with a history of the first ever ischemic stroke (6 months and more after stroke onset), which was neuroradiologically confirmed, were studied. These were compared to 30 hypertensive patients without history of any cardiovascular event, being of similar age and sex. BRS and BRSf were determined by the sequence and spectral methods (fiveminute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). A significant negative correlation between spontaneous BRS and blood pressure (BP) represented by the grade of hypertension was present (r = -0.52, p<0.001). Differences between hypertensives with and without stroke were detected in BRS obtained by the spectral method (BRS spect p=0.0237, BRSf spect p=0.0285) or BRS obtained by sequence method (BRS seq p=0.0532, BRSf seq p=0.0273). The greatest decline in BRS values was in hypertensive stroke patients with metabolic syndrome, who had BRS values below 3 ms/mm Hg. We found out that BRS and BRSf were more impaired in stroke patients with essential hypertension even 6 months and more after stroke onset than in stroke-free hypertensive patients. This finding was independent of age-dependent decrease of BRS. Examination of baroreflex sensitivity as a marker of autonomic dysfunction along with global cardiovascular risk stratification of individuals seems to be a method for identifying patients at high residual cardiovascular risk., D. Čelovská ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The skin matrix metalloproteinase 3, tissue inhibitors of matrix metalloproteinase 2 and collagen III content changes in type 1 diabetes and insulin resistance treated with insulin a nd metformin were studied. Healthy adult male Wistar rats were obtained from experimental animal house, Department of Experimental Pharmacology, Medical University in Bialystok. The rats were divided randomly into five groups of 8 rats each. Control rats were injected intraperitoneally by NaCl. Type IDDM was induced by a single injection of Streptozocin. Insulin resistance was induced by a high -fat diet. The chosen groups of rats were also treated with insulin or metformin. ELISA K its (USCN Life Science, China) were used to measure content of matrix metallo - proteinase 3 (ELISA Kit for Matrix Metalloproteinase 3 - MMP3), tissue inhibitor of matrix metalloproteinase 2 (ELISA Kit for Tissue Inhibitors of Metalloproteinase 2 - TIMP2) and content of collagen type 3 (ELISA Kit for Collagen Type III - COL3). The results were reported as a median. The statistical significance was defined as p<0.05. Type 1 diabetes and insulin resistance have significantly reduced the quality of the skin, shown by the increase in cont ent of matrix metalloproteinase 3 and the decrease in content of tissue inhibitors of matrix metalloproteinase 2. Type 1 diabetes and insulin resistance have reduced the quality of the skin expressed by type III collagen content decrease but for future studies it is recommend to determine rat interstitial collagenase, MMP -13, as well. Insulin and metformin treatment improved the quality of the diabetic skin, demonstrated by the type III collagen content increase., M. Knaś, K. Wołosik, A. Zalewska, A. Mikucka-Niczyporuk, I. Kasacka, M. Niczyporuk., and Obsahuje bibliografii
The transformed C6 glial cells in cultures were treated with sodium mercaptoborate (Na2B12H11SH, BSH), a carrier of atomic targets (10B) of thermal neutrons for the neutron capture therapy of brain tumors. As shown by light microscopy, the therapeutic dose of BSH (100 µg/ml) did not alter the gross morphology and growth of the population of cells within a 72 h treatment interval. Electron microscopic analysis of these cells revealed activation of nucleoli and, occasionally, enlarged and bifurcated mitochondria. After 200 µg BSH/ml and 72 h treatment, growth of the cell population was inhibited and ultrastructural changes became more profound. They included condensation of chromatin and its allocation to the nuclear envelope which formed deeper invaginations. Mitochondria further increased in size and were characterized by slim or angular cristae. Moreover, in circumscribed segments of some of the slightly swollen mitochondria their cristae disappeared or were reduced to fine pouch-like structures localized near the continuous outer membrane, suggestive for a non-destructive restructuring of the inner mitochondrial membrane. The smooth pinocytotic vesicles near the plasma membrane, lysosomes and heterogeneous dense bodies were more frequent. The revealed subcellular targets of BSH may initiate the development of pharmacological protocols aimed to further improve the tolerance to BSH by the healthy tissues of patients undergoing BNCT of brain tumors, e.g. by intervention into the oxidative stress triggered likely by the altered mitochondria., V. Mareš, D. Krajčí, V. Lisá., and Obsahuje bibliografii
Prolonged agonist stimulation results in specific transfer of activated Gα subunits of Gqα/G11α family from particulate membrane fraction to soluble (cytosol) cell fraction isolated as 250 000 x g supernatant. In this study, we have used 2D electrophoresis for more defined resolution of Gα subunits of Gqα/G11α family and followed the time course of solubilization effect. The small signal of soluble G proteins was already detected in control, hormone-unexposed cells. Hormone stimulation resulted in a slow but continuous increase of both intensity and number of immunoreactive signals/spots of these G proteins (10, 30, 60, 120 and 240 min). At longer times of agonist exposure (>2 hours), a marked increase of Gqα/G11α proteins was detected. The maximal level of soluble Gqα/G11α proteins was reached after 16 hours of continuous agonist exposure. At this time interval, eight individual immunoreactive signals of Gqα/G1 α proteins could be resolved. The relative proportion among these spots was 15:42:10:11:7:7:2:5. Solubilization of this class of Gα proteins was thus observed after prolonged agonist stimulation only, induced by ultra high concentration of hormone and in cells expressing a large number of GPCRs. Our data therefore rather indicate tight/persisting binding of Gqα/G11α proteins to the membrane., D. Durchánková, J. Novotný, P. Svoboda., and Obsahuje bibliografii a bibliografické odkazy