Induction of the inducible form of nitric oxide synthase (iNOS) in the vascular and cardiac tissue by several inflammatory stimuli may result in the production of large amounts of nitric oxide (NO) for a sustained period. Recent data obtained in the rat aorta in which iNOS was induced by lipopolysaccharide (LPS) have demonstrated that adventitial cells represent the main site of NO production. Adventitial-derived NO can exert an immediate down-regulatory effect on smooth muscle contraction (via activation of the cyclic GMP pathway) but may also initiate longer lasting effects through the formation of NO stores within the medial layer. One candidate for such NO stores are dinitrosyl non-heme iron complexes. Low molecular weight thiols interact with preformed NO stores and promote vasorelaxation by a cyclic GMP-independent mechanism involving the activation of potassium channels. In the heart, the induction of iNOS is involved in delayed protection against ischemia-reperfusion-induced functional damages. Recent data obtained with monophosphoryl lipid A, a non-toxin derivative of LPS, strongly suggest that iNOS-derived NO in the rat heart does not act as an immediate mediator of the cardioprotection but rather as a trigger of long-term protective mechanisms. Thus, the present data reveal the important role of adventitial cells as a site of iNOS expression and activity in intact blood vessels. The induction of adaptive mechanisms in the heart and the formation of releasable NO stores in blood vessels are examples of long-term consequences of iNOS induction. These new information are relevant for a better understanding of the circumstances in which NO overproduction by iNOS may play either a beneficial or deleterious role in these tissues., B. Muller, A. L. Kleschyov, K. Gyorgy, J.-C. Stoclet., and Obsahuje bibliografii
Angiogenesis is known to be triggered by various stimuli including hypertension. It was previously found that NO-deficient hypertension is accompanied by structural remodeling of the cardiac muscle and large coronary arteries. This study was aimed to examine the qualitative subcellular alterations of capillaries in the heart of the rats treated with L-NAME (40 mg/kg/day for 4 weeks). The results showed that long-lasting inhibition of NO production induced an apparent activation of fibroblast function. This was associated with enhancement of fibrozation as well as with the induction of angiogenesis. Accordingly, fibroblasts were frequently located in the vicinity of capillary pericytes, which was followed by their detachment and migration. Moreover, besides inactive or even injured capillaries, the other ones exhibited extensive proteosynthetic activity linked to capillary growth, proliferation and migration of endothelial cells. The results strongly indicate enhanced triggering of the angiogenesis in L-NAME-induced NO-deficient hypertension., Ľ. Okruhlicová, N. Tribulová, I. Bernátová, O. Pecháňová., and Obsahuje bibliografii
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-α and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-α (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71- 1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35±1.42 vs. 5.97±1.29 109 l); APA vs. IHA: TNF-α (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63- 1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37±1.41 vs. 5.71±1.21 109 l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] μg/l, p≤0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA., Z. Šomlóová, O. Petrák, J. Rosa, B. Štrauch, T. Indra, T. Zelinka, M. Haluzík, V. Zikán, R. Holaj, J. Widimský Jr., and Obsahuje bibliografii
The present study was undertaken to evaluate the use of cortisol 6b-hydroxylation in defining the effect of amiodarone on cytochrome CYP3A activity. To accomplish this goal, the in vivo activity of CYP3A was estimated by measuring the 24-hour urinary excretion of 6b-hydroxycortisol (6b-OHC) and by calculating 24-hour ratio of 6b-hydroxycortisol to urinary free cortisol (6b-OHC/UFC ratio). Nine cardiac patients scheduled for amiodarone treatment were recruited to participate in this study. Urine was collected over a 24-hour period from each subject before the first amiodarone administration and during the third day of oral administration of amiodarone (200 mg four times daily as a loading dose). Three days of amiodarone treatment caused a significant decrease (p<0.05) in both the 6b-OHC/UFC ratio and the 24-hour urinary excretion of 6b-OHC. These results suggest that amiodarone is an inhibitor of CYP3A activity., S. Mičuda, M. Hodač, L. Šišpera, P. Pařízek, M. Pleskot, G. Zimová, J. Cerman, J. Martínková, V. Pinderman., and Obsahuje bibliografii
We studied the effects of administration of b-resorcylidene aminoguanidine (RAG) to Wistar strain rats with experimental diabetes mellitus (DM) induced by streptozotocin. The effects studied included antioxidant levels in plasma and the liver, oxidative damage of lipids represented by the formation of substances reacting with thiobarbituric acid (TBARP) and selected biochemical indicators. The administration of RAG did not significantly affect antioxidant status of diabetic rats or hemoglobin glycation and plasma concentration of fructosamine. In diabetic rats, application of RAG decreased formation of TBARP in plasma but not in the liver. Moderate steatosis of liver and increased plasma levels of triacylglycerols in diabetic rats were significantly improved by application of RAG., A. Liptáková, J. Čársky, O. Uličná, O. Vančová, P. Božek, Z. Ďuračková., and Obsahuje bibliografii
The myocardium examination by MR spectroscopy is very challenging due to movements caused by the cardiac rhythm and breathing. The aim of the study was to investigate the influence of breathing on the quantitative measurement of lipid/water ratios in different groups of volunteers and different measuring protocols. We examined the lipid content of myocardium at 3T using the proton single voxel spectroscopy. Three protocols (free breathing, breath hold and the use of respiratory navigator) controlled by ECG were used for t he examination of 42 adult volunteers including 14 free divers. Spectra were evaluated using jMRUI software. An average content of lipids in the healthy interventricular septum, gained by all protocols was equal to 0.6 %, which is in agreement with other p ublished data. Based on the quality of examinations and the highest technical success, the best protocol seems to be the one containing a respiratory navigator since it is more acceptable by patients. Based on our results and the literature data we can con clude that MR spectroscopy is able to distinguish patients from controls only if their myocardial lipid content is higher than 1.6 % (mean value of lipids plus two standard deviations)., M. Drobny, P. Sedeivy, M. Dezortova, D. Wagnerova, M. Hajek., and Obsahuje bibliografii
Poly-(lactide-co-glycolide) (PLGA) is an FDA-approved biodegradable polymer which has been widely used as a scaffold for tissue engineering applications. Collagen has been used as a coating material for bone contact materials, but relatively little interest has focused on biomimetic coating of PLGA with extracellular matrix components such as collagen and the glycosaminoglycan chondroitin sulfate (CS). In this study, PLGA films were coated with collagen type I or collagen I with CS (collagen I/CS) to investigate the effect of CS on the behaviour of the osteoblastic cell line MG 63. Collagen I/CS coatings promoted a significant increase in cell number after 3 days (in comparison to PLGA) and after 7 days (in co mparison to PLGA and collagen-coated PLGA). No influence of collagen I or collagen I/CS coatings on the spreading area after 1 day of culture was observed. However, the cells on collagen I/CS formed numerous filopodia and displayed well developed vinculin-containing focal adhesion plaques. Moreover, thes e cells contained a significantly higher concentration of osteocalcin, measured per mg of protein, than the cells on the pure collagen coating. Thus, it can be concluded that collagen I/CS coatings promote MG 63 cell proliferation, improve cell adhesion and enhance osteogenic cell differentiation., M. Vandrovcová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The effects of inclusion of sesamin / episesamin in Baltic Atlantic salmon ( Salmo salar L.) diets based on vegetable oils were studied. The study was designed as a dose response study with two control diets, one diet based on fish oil (FO) and one diet based on a mixture of linseed and sunflower oil (6:4 by vol.) (MO). As experimental diets three different levels of inclusion of sesamin / episesamin (hereafter named sesamin) to the MO based diet and one diet based on sesame oil and linseed oil (SesO) (1:1 by vol.) were used. Th e dietary oils were mirrored in the fatty acid profile of the white muscle. Sesamin significantly decreased the levels of 18:3n-3 in the white muscle phospholipid (PL) fraction of all groups fed sesamin, no significant differences were found in the triacylglycerol fraction (TAG). Slightly increased levels of docosahexaenoic acid (22:6n-3, DHA) in PL and TAG were found in some of the sesamin fed groups. Sesamin significantly affected the expressi on of peroxisome proliferator- activated receptor α , scavenger receptor type B and hormone sensitive lipase, in agreement wi th previous studies on rainbow trout ( Oncorhynchus mykiss ) and Atlantic salmon ( Salmo salar L.) hepatocytes published by our group. No significant effects on toxicological response measured as ethoxyresorufin O-deethylase activity was found. The total cytochrome P450 enzymes were significantly higher in MO 0.29 and SesO group. The amount of α - and γ -tocopherols in liver and the amount of γ -tocopherol in white muscle were significantly lower in fish fed the FO diet compared to the MO diet, but no difference after inclusion of sesamin was found in this study. Increased inclusion of sesamin increased the levels of sesamin and episesamin in the liver, but did not affect the amounts in white muscle., S. Trattner ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Oxygen supply was corrected in rabbits during the hepatic ischemia/reperfusion by means of different breathing mixtures: hypoxic (14.8 % O2+85.2 % N2), hyperoxic (78 % O2+20.2 % N2+ 1.8 % CO2), or hypercapnic (5 % CO2 in air). Hepatic ischemia was induced for 30 min by ligation of hepatic artery, reperfusion period lasted 120 min. Indices of blood oxygen transport (p50act, pCO2, pH, pO2, etc.) and prooxidant-antioxidant balance (Schiff bases, conjugated dienes, catalase, retinol, a-tocopherol) were measured in the blood and liver. The severity of reperfusion damage was evaluated by the activities of alanine and aspartate aminotransferases (ALT, AST) in the blood. Hepatic ischemia/reperfusion resulted in higher p50act in hepatic venous and mixed venous blood in all experimental groups. The changes of p50act were most marked in the hypercapnic group and were the weakest in the hypoxic group. The rise in p50act was accompanied by higher levels of lipid peroxidation products, ALT and AST in blood and liver homogenates, and by a simultaneous fall of α-tocopherol and retinol concentrations, except in the hypoxic group. Catalase activity at the end of reperfusion increased under normoxia, decreased under hyperoxia or hypercapnia and did not change under hypoxia. The moderate hypoxia during reperfusion was accompanied by a better balance between the mechanisms of reactive oxygen species production and inactivation that may be observed by optimal changes in p50act and reduced the hepatic damage in this pathological condition., V. V. Zinchuk, M. N. Khodosovsky, D. A. Maslakov., and Obsahuje bibliografii