The adrenal glands produce significant amounts of steroid hormones and their metabolites, with various levels of androgenic activities. Until recently, the androgenic potency of these adrenal-derived compounds were not well known, but some recent studies have shown that the production of 11-oxoand 11β-hydroxy-derived testosterone and dihydrotestosterone evidently have high androgenic activity. This fact has clinical importance, for instance, in various types of congenital adrenal hyperplasia with androgenization or polycystic ovarian syndrome, and laboratory determinations of these substances could help to better evaluate the total androgen pressure in patients with these disorders. Another area of concern is the treatment of prostate cancer with androgen deprivation, which loses effectiveness after a certain time. The concurrent blocking of the secretion of adrenal C19-steroids, whether using corticoids or adrenostatics, could increase the effectiveness of androgen-deprivation therapy., Luboslav Stárka, Michaela Dušková, Jana Vítků., and Obsahuje bibliografii
The 14-3-3 proteins are a family of acidicr egulatory molecules found in all eukaryotes. 14-3-3 proteins function as molecular scaffolds by modulating the conformation of their binding partners. Through the functional modulation of a wide range of binding partners, 14-3-3 proteins are involved in many processes including cell cycle regulation, metabolism control, apoptosis, and control of gene transcription. This minireview includes a short overview of 14-3-3 proteins and then focuses on their role in the regulation of two important binding partners: FOXO forkhead transcription factors and an enzyme tyrosine hydroxylase., V. Obšilová, J. Šilhan, E. Bouřa, J. Teisinger, T. Obšil., and Obsahuje bibliografii a bibliografické odkazy
Our own study as well as others have previously reported that hypoxia activates 15-lipoxygenase (15-LO) in the brain, causing a series of chain reactions, which exacerbates ischemic stroke. 15-hydroxyeicosatetraenoic acid (15-HETE) and 15-oxoeicosatetraenoic acid (15-oxo-ETE/15-KETE) are 15-LO-specific metabolites of arachidonic acid (AA). 15-HETE was found to be rapidly converted into 15-oxo-ETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in some circumstances. We have demonstrated that 15-HETE promotes cerebral vasoconstriction during hypoxia. However, the effect of 15-oxo-ETE upon the contraction of cerebral vasculature remains unclear. To investigate this effect and to clarify the underlying mechanism, we performed immunohistochemistry and Western blot to test the expression of 15-PGDH in rat cerebral tissue, examined internal carotid artery (ICA) tension in isolated rat ICA rings. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of voltage-gated potassium (Kv) channels (Kv2.1, Kv1.5, and Kv1.1) in cultured cerebral arterial smooth muscle cells (CASMCs). The results showed that the levels of 15-PGDH expression were drastically elevated in the cerebral of rats with hypoxia, and 15-oxo-ETE enhanced ICA contraction in a dose-dependent manner. This effect was more significant in the hypoxic rats than in the normoxic rats. We also found that 15-oxo-ETE significantly attenuated the expression of Kv2.1 and Kv1.5, but not Kv1.1. In conclusion, these results suggest that 15-oxo-ETE leads to the contraction of the ICA, especially under hypoxic conditions and that specific Kv channels may play an important role in 15-oxo- ETE-induced ICA constriction., Di Wang, Yu Liu, Ping Lu, Daling Zhu, Yulan Zhu., and Obsahuje bibliografii
a1_Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI)., a2_We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD., Magdaléna Kovářová, Zuzana Žilinská, Ján Páleš, Zuzana Kužmová, Andrea Gažová, Juraj Smaha, Martin Kužma, Peter Jackuliak, Viera Štvrtinová, Ján Kyselovič, Juraj Payer., and Obsahuje bibliografii
3D microscopy and image analysis provide reliable measurements of length, branching, density, tortuosity and orientation of tubular structures in biological samples. We present a survey of methods for analysis of large samples by measurement of local differences in geometrical characteristics. The methods are demonstrated on the structure of the capillary bed in a rat brain., J. Janáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The lipophilic cationic radiotracer 99m Tc-sestamibi, known to be concentrated within mitochondria, is widely used for myocardial perfusion and to a lesser extent for muscle metabolism imaging. However, the exact distribution pattern in skeletal muscle has not been yet studied in detail. The present study aims to investigate the 99m Tc-sestamibi uptake in rat skeletal muscle and myocardium in relation to their metabolic characteristics. 99m Tc-sestamibi was i.v. administered in twenty adult male Wistar rats and uptake, as percent of injected dose per tissue gram (%ID/g), in the myocardium, soleus, extensor digitorum longus and gastrocnemius muscles was assessed 2 h after the injection. Muscle uptake was also correlated with myocardial uptake, muscle weight and body weight. Skeletal muscle 99m Tc-sestamibi uptake was a small (9-16 %) fraction of that found in myocardium (1.71 ± 0.63 %ID/g). Among the three hindlimb muscles considered, the slow-oxidative soleus muscle showed the highest uptake (0.28 ± 0.16 %ID/g). Metabolically diverse parts of the gastrocnemius muscle showed different uptake. Skeletal muscle uptake was positively correlated with myocardial uptake and both were negatively correlated with tissue and body weight. Skeletal muscle and myocardium 99m Tc-sestamibi uptake is related to their metabolic profile. Myocardium, with an exceptional rich mitochondrial concentration, shows much higher 99m Tc-sestamibi uptake compared to skeletal muscles. Among muscles, uptake is dependent on their mitochondrial content. Evidence of matching exists between myocardial and muscle uptake, and both are size-dependent., G. Arsos ... [et al.]., and Obsahuje seznam literatury
The binding of [3H]SCH 23390 has been studied in various brain regions of male mice with the experience of repeated victory (winners) or defeat (losers) gained over 10 (T10) and 20 (T20) days of daily agonistic confrontations. In the frontal cortex, Bmax of [3H]SCH 23390 binding sites was found to be increased in T10 losers and decreased in T20 losers when compared to the control mice. In the striatum, T10 and T20 winners had reduced values of [3H]SCH 23390 binding sites than the ones in the control mice. The Kd was increased in the frontal cortex of T10 losers and T10 winners as well as in the amygdala of T20 losers. Reduced Kd values were found in the striatum of all experimental groups as well as in the amygdala of T20 winners. Thus, both specific changes relating to social behavior patterns and non-specific ones in [3H]SCH 23390 binding were found in the brain regions of mice after 10 and 20 days of intermale confrontations., D. F. Avgustinovich, O. V. Alekseyenko., and Obsahuje bibliografii a bibliografické odkazy
Elevated levels of eukaryotic initiation factor 4E (eIF4E) are implicated in neoplasia, with cumulative evidence pointing to its role in the etiopathogenesis of hematological diseases. As a node of convergence for several oncogenic signaling pathways, eIF4E has attracted a great deal of interest from biologists and clinicians whose efforts have been targeting this translation factor and its biological circuits in the battle against leukemia. The role of eIF4E in myeloid leukemia has been ascertained and drugs targeting its functions have found their place in clinical trials. Little is known, however, about the pertinence of eIF4E to the biology of lymphocytic leukemia and a paucity of literature is available in this regard that prospectively evaluates the topic to guide practice in hematological cancer. A comprehensive analysis on the significance of eIF4E translation factor in the clinical picture of leukemia arises, therefore, as a compelling need. This review presents aspects of eIF4E involvement in the realm of the lymphoblastic leukemia status; translational control of immunological function via eIF4E and the state-of-the-art in drugs will also be outlined., V. Venturi, T. Masek, M. Pospisek., and Obsahuje bibliografii
Reactive hyperemia (RH) in forearm muscle or skin microcirculation has been considered as a surrogate endpoint in clinical studies of cardiovascular disea e. We evaluated two potential confounders that might limit such use of RH, namely laterality of measurement and intake of non-steroidal anti-inflammatory drugs (NSAIDS). Twenty-three young non-smoking healthy adults were enrolled. In Experiment 1 (n=16), the RH elicited by 3 min of ischemia was recorded in the muscle (strain gauge plethysmography, hand excluded) and skin (laser Doppler imaging) of both forearms. In Experiment 2 (n=7), RH was determined in the dominant forearm only, one hour following oral acetylsalicylic acid (1 g) or placebo. In Experiment 1, peak RH was identical in both forearms, and so were the corresponding durations of responses. RH lasted significantly less in muscle than in skin (p=0.003), a hitherto unrecognized fact. In the skin, acetylsalicylate reduced duration (43 vs. 57.4 s for placebo, p=0.03), without affecting the peak response. In muscle, duration tended to decrease with acetylsalicylate (21.4 vs. 26.0 s with placebo, p=0.06) and the peak increase in blood flow was blunted (27.2 vs. 32.4 ml/min/100 ml tissue with placebo, p=0.003). We conclude that, when using RH as a surrogate endpoint in studies of cardiovascular disease, a confounding by laterality of measurement need not be feared, but NSAIDS may have an influence, although perhaps not on the peak response in the skin., G. Addor, A. Delachaux, B. Dischl, D. Hayoz, L. Liaudet, B. Waeber, F. Feihl., and Obsahuje bibliografii a bibliografické odkazy
To determine whether PHEMA [poly(2-hydroxyethylmethacrylate)] is suitable for portal vein embolization in patients scheduled to right hepatectomy and whether it is as effective as the currently used agent (a histoacryl/lipiodol mixture). Two groups of nine patients each scheduled for extended right hepatectomy for primary or secondary hepatic tumor, had right portal vein embolization in an effort to induce future liver remnant (FLR) hypertrophy. One group had embolization with PHEMA, the other one with the histoacryl/lipiodol mixture. In all patients, embolization was performed using the right retrograde transhepatic access. Embolization was technically successful in all 18 patients, with no complication related to the embolization agent. Eight patients of either group developed FLR hypertrophy allowing extended right hepatectomy. Likewise, one patient in each group had recanalization of a portal vein branch. Hist ology showed that both embolization agents reach the periphery of portal vein branches, with PHEMA penetrating somewhat deeper into the periphery. PHEMA has been shown to be an agent suitable for embolization in the portal venous system comparable with existing embolization agent (histoacryl/lipiodol mixture)., J. H. Peregrin, R. Janoušek, D. Kautznerová, M. Oliverius, E. Sticová, M. Přádný, J. Michálek., and Obsahuje bibliografii
The aim of this study was to investigate the effects of troglitazone (TRO) - a new insulin-sensitizing agent - on some metabolic parameters in an experimental model of hypertriglyceridemia and insulin resistance, hereditary hypertriglyceridemic rats, and to compare its effects with those of vitamin E, an antioxidant agent. Three groups of the above rats were fed diets with a high content of sucrose (70 % of energy as sucrose) for four weeks. The first group was supplemented with TRO (120 mg/kg diet), the second one with vitamin E (500 mg/kg diet), and the third group served as the control. Vitamin E supplementation did not lower serum triglycerides (2.42±0.41 vs. 3.39±0.37 mmol/l, N.S.) while TRO did (1.87±0.24 vs. 3.39±0.37 mmol/l, p<0.01). Neither TRO nor vitamin E influenced the serum levels of free fatty acids (FFA). Both drugs influenced the spectrum of fatty acids in serum phospholipids - TRO increased the levels of polyunsaturated fatty acids (PUFA) n-6 (36.04±1.61 vs. 19.65±1.56 mol %, p<0.001), vitamin E increased the levels of PUFA n-3 (13.30±0.87 vs. 6.79±0.87 mol %, p<0.001) and decreased the levels of saturated fatty acids (32.97±0.58 vs. 51.45±4.01 mol %, p<0.01). In conclusion, TRO lowered the level of serum triglycerides but vitamin E did not have this effect in hypertriglyceridemic rats. Compared with TRO, vitamin E had a different effect on the spectrum of fatty acids in serum phospholipids., Š. Chvojková, L. Kazdová, J. Divišová., and Obsahuje bibliografii
The correlation between baroreflex sensitivity (BRS) and the spectrum component at a frequency of 0.1 Hz of pulse intervals (PI) and systolic blood pressure (SBP) was studied. SBP and PI of 51 subjects were recorded beat-to-beat at rest (3 min), during exercise (0.5 W/kg of body weight, 9 min), and at rest (6 min) after exercise. BRS was determined by a spectral method (a modified alpha index technique). The subjects were divided into groups according to the spectral amplitude of SBP at a frequency of 0.1 Hz. The following limits of amplitude (in mm Hg) were used: very high ≥ 5.4 (VH); high 5.4 > H ≥ 3 (H); medium 3 > M ≥ 2 (M), low < 2 (L). We analyzed the relationships between 0.1 Hz variability in PI and BRS at rest, during the exercise and during recovery in subgroups VH, H, M, L. The 0.1 Hz variability of PI increased significantly with increasing BRS in each of the groups with identical 0.1 Hz variability in SBP. This relationship was shifted to the lower values of PI variability at the same BRS with a decrease in SBP variability. The primary SBP variability increased during exercise. The interrelationship between the variability of SBP, PI and BRS was identical at rest and during exercise. A causal interrelationship between the 0.1 Hz variability of SBP and PI, and BRS was shown. During exercise, the increasing primary variability in SBP due to sympathetic activation was present, but it did not change the relationship between variability in pulse intervals and BRS., N. Honzíková, A. Krtička, Z. Nováková, E. Závodná., and Obsahuje bibliografii
Uric acid is the final product of human purine metabolism. It was pointed out that this compound acts as an antioxidant and is able to react with reactive oxygen species forming allantoin. Therefore, the measurement of allantoin levels may be used for the determination of oxidative stress in humans. The aim of the study was to clarify the antioxidant effect of uric acid during intense exercise. Whole blood samples were obtained from a group of healthy subjects. Allantoin, uric acid, and malondialdehyde levels in plasma and erythrocytes were measured using a HPLC with UV/Vis detection. Statistical significant differences in allantoin and uric acid levels during short-term intense exercise were found. Immediately after intense exercise, the plasma allantoin levels increased on the average of 200 % in comparison to baseline. Plasma uric acid levels increased slowly, at an average of 20 %. On the other hand, there were no significant changes in plasma malondialdehyde. The results suggest that uric acid, important antioxidant, is probably oxidized by reactive oxygen species to allantoin. Therefore allantoin may be suitable candidate for a marker of acute oxidative stress., R. Kanďár, X. Štramová, P. Drábková, J. Křenková., and Obsahuje bibliografii
There is increasing evidence that dietary saturated fatty acids (SAFA) have not only an indirect atherogenic effect due to increasing LDL-cholesterol concentration but also a direct effect by activating the inflammation process. This review summarizes several recent publications in this field. The effect of SAFA on the inflammation process mediated by Toll-like receptor 4/NF-κB pathway has been well documented in various in vitro culture studies of macrophages and adipocytes or in their co-culture. In contrast to these in vitro data, in vivo epidemiological studies or clinical experiments in men are less consistent. Well controlled cross-over studies in volunteers might enlighten the differences between saturated and unsaturated fatty acids dietary intake and proatherogenic inflammation effects., R. Poledne., and Obsahuje seznam literatury
Experimental data concerning the bioavailability of the different Mg-salts in human organism is inconsistent. Mg-absorption reported by clinical studies largely varies depending on the method used for evaluation. The aim of this study was to evaluate the bioavailability and accessibility of magnesium bound in different Mg-salt compounds, using an in vitro model of intestinal cell barrier. The study included a variety of inorganic (oxide, sulphate, chloride, carbonate) and organic salts (lactate, citrate, pidolate). Caco-2 cells were cultivated in a complete culture medium with different magnesium salts treatments in ascending concentrations. The viability and quantity of cells was analysed by FACS. Mg-absorption was analysed by a direct colorimetric assay, measured by spectrometry. T-test identified a significant decrease in cell count treatment with mg-lactate compared with citrate. Mg-pidolate showed a significantly higher cell viability compared with Mg-citrate, Mg-lactate and Mg-chloride. Even though the difference was not significant, we showed that an increase in Mg2+ salt concentration progressively decreased the cell count and the viability and the effect was universal for all the used Mg-salt treatments. Mg-citrate, chloride, and sulphate showed a significantly lower absorption compared to Mg-carbonate, pidolate and oxide. Our in vitro monolayer model of human intestinal transport showed that viability and quantity of cell decreased with increasing Mg-concentration. We admit that our experiment model may have some limitations in accurately describing an in vivo Mg2+ absorption. Moreover, it is also necessary to assess the relevance of our data in vivo and especially in clinical practice., Ján Kyselovič, Nikola Chomaničová, Adriana Adamičková, Simona Valášková, Barbara Šalingová, Andrea Gažová., and Obsahuje bibliografii
Together with the development of peritoneal dialysis (PD), appropriate animal models play an important role in the investigation of physiological, pathophysiological and clinical aspects of PD. However, there is still not an ideal experimental PD animal model. In this study, 45 Sprague-Dawley rats were divided into three groups. Grou p 1 (n=15) was receiving daily peritoneal injection through the catheter connected to the abdominal cavity, using PD solution containing 3.86 % D-glucose. Group 2 (n=15) was receiving daily peritoneal injection of 0.9 % physiological saline through a catheter. Group 3 (n=15), which was subjected to sham operation, served as controls. Our results showed that WBC counts in peritoneal effluent of Group 1 were slightly higher than those of Group 2 and control group, respectively (p<0.05). However, there was no episode of infection in any group. In addition, there was no significant difference in neutrophils fractions among these three groups. Hematoxylin-eosin and Masson’s trichrome staining demonstrated a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum exposed to high glucose (Group 1) compared to Group 2 and controls (p<0.01). These data indicated that we established a novel rat model of PD with a modified catheter insertion method. This model is more practical, easy to operate, not too expensive and it will facilitate the investigate of long-term effects of PD., Y.-M. Peng ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of the present work was to study the effect of 3- mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo . In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by Vmax value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC50 values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 μM CMTI was recorded (I=0.9±2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications., M. Soltesova Prnova, J. Ballekova, A. Gajdosikova, A. Gajdosik, M. Stefek., and Obsahuje bibliografii
Endothelin B (ETB) receptors present in abundance the central nervous system (CNS) have been shown to have significant implications in its development and neurogenesis. We have targeted ETB receptors stimulation using a highly specific agonist, IRL-1620, to treat CNS disorders. In a rat model of cerebral ischemia intravenous administration IRL-1620 significantly reduced infarct volume and improved neurological and motor functions compared to control. This improvement, in part, is due to an increase in neuroregeneration. We also investigated the role of IRL-1620 in animal models of Alzheimer’s disease (AD). IRL-1620 improved learning and memory, reduced oxidative stress and increased VEGF and NGF in Aβ treated rats. IRL-1620 also improved learning and memory in an aged APP/PS1 transgenic mouse model of AD. These promising findings prompted us to initiate human studies. Successful chemistry, manufacturing and control along with mice, rat and dog toxicological studies led to completion of a human Phase I study in healthy volunteers. We found that a dose of 0.6 μg/kg of IRL-1620 can be safely administered, three times every four hours, without any adverse effect. A Phase II clinical study with IRL-1620 has been initiated in patients with cerebral ischemia and mild to moderate AD., A. Gulati, M. G. Hornick, S. Briyal, M. S. Lavhale., and Seznam literatury
Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and ε -caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47±10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35±9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the develo pment of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts., I. Skalský ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an in ducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G>C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstr ated lower frequencies of the CC genotype (P=0.005). From th e DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1>10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G>C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequenc ies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G>C polymorphism with the risk of DN., J. A. Hubáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Chronic sojourn in hypoxic environment results in the structural remodeling of peripheral pulmonary arteries and pulmonary hypertension. We hypothesize that the pathogenesis of changes in pulmonary vascular structure is related to the increase of radical production induced by lung tissue hypoxia. Hypoxia primes alveolar macrophages to produce more hydrogen peroxide. Furthermore, the increased release of oxygen radicals by other hypoxic lung cells cannot be excluded. Several recent reports demonstrate the oxidant damage of lungs exposed to chronic hypoxia. The production of nitric oxide is high in animals with hypoxic pulmonary hypertension and the serum concentration of nitrotyrosine (radical product of nitric oxide and superoxide interaction) is also increased in chronically hypoxic rats. Antioxidants were shown to be effective in the prevention of hypoxia induced pulmonary hypertension. We suppose that the mechanism by which the radicals stimulate of the vascular remodeling is due to their effect on the metabolism of vascular wall matrix proteins. Non-enzymatic protein alterations and/or activation of collagenolytic matrix metalloproteinases may also participate. The presence of low-molecular weight cleavage products of matrix proteins stimulates the mesenchymal proliferation in the wall of distal pulmonary arteries. Thickened and less compliant peripheral pulmonary vasculature is then more resistant to the blood flow and the hypoxic pulmonary hypertension is developed., J. Herget, J. Wilhelm, J. Novotná, A. Eckhardt, R. Vytášek, L. Mrázková, M. Ošťádal., and Obsahuje bibliografii
The purpose of the present study was to examine the role of the T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism on changes in renal hemodynamics and blood pressure due to Na+ loading. Twenty-eight older (63±1 years), moderately obese (39±2 % fat) hypertensives had th eir glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and plasma nitric oxide (NOx) levels determined after eight days of low (20 mEq) and high (200 mEq) Na+ diets. The two Na+ diets were separated by a 1-week washout period. Subjects were genotyped for the eNOS-786 site and were grouped on whether they were homozygous or heterozygous for the C allele (TC+CC, n=13) or only homozygous for the T allele (TT, n=15). The TC+CC genotype group had a significantly greater increase in diastolic (P=0.021) and mean arterial (P=0.018) BP and a significant decline in both RPF (P=0.007) and GFR (P=0.029) compared to the TT genotype group with Na+ loading. Furthermore, Na+ loading resulted in a significant (P=0.036) increase in plasma NOx in the TT, but not in the TC+CC genotype group as well as a trend (P=0.051) for an increase in urine NOx in TC+CC, but not in the TT genotype group. The increase in BP during Na+ loading in older hypertensives was associated with the eNOS genotype and may be related to changes in renal hemodynamics due to changes in NO metabolism., D. R. Dengel, M. D. Brown, R. E. Ferrell, T. H. Reynolds, M. A. Supiano., and Obsahuje bibliografii a bibliografické odkazy
Hypoxic pulmonary vasoconstric tion (HPV) is an important homeostatic mechanism in which increases of [Ca2+] i are primary events. In this study, primary cultured, human pulmonary artery smooth muscle cells (hPASMC) were used to examine the role of TRPC channels in mediating [Ca2+] i elevations during hypoxia. Hypoxia (PO2 about 20 mm Hg) evoked a transient [Ca2+] i elevation that was reduced by removal of extracellular calcium. Nifedipine and verapamil, blockers of vo ltage-gated calcium channels (VGCCs), attenuated th e hypoxia-induced [Ca2+] i elevation by about 30 %, suggesting the presence of alternate Ca2+ entry pathways. Expression of TRPC1 an d TRPC6 in hPASMC were found by RT-PCR and confirmed by Western blot analysis. Antagonists for TRPC, 2APB and SKF96365, significantly reduced hypoxia-induced [Ca2+] i elevation by almost 60 %. Both TRPC6 and TRPC1 were knocked down by siRNA, the loss of TRPC6 decreased hypoxic response down to 21 % of control, whereas the knockdown of TRPC1 reduced the hypoxia respon se to 85 %, suggesting that TRPC6 might play a central role in mediating hypoxia response in hPASMC. However, blockade of PLC pathway caused only small inhibition of the hypoxia response. In contrast, AICAR, the agonist of AMP-activated kinase (AMPK), induced a gradual [Ca2+] i elevation, whereas compound C, an antagonist of AMPK, almost abolished the hypoxia response. Ho wever, co-immunoprecipitation revealed that AMPK α was not colocalized with TRPC6. Our data supports a role for TRPC6 in mediation of the [Ca2+] i elevation in response to hypoxia in hPASMC and suggests that this response may be linked to cellular energy status via an activation of AMPK., C. Tang, W. K To, F. Meng, Y. Wang, Y. Gu., and Obsahuje bibliografii
Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2 - production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat., M. M. Govender, A. Nadar., and Obsahuje bibliografii
The purpose of this study was to determine if there is flowmediated vasodilation of the femoral artery in response to progressive increases in flow within a physiological range observed in the in vivo experiments. Femoral artery blood flow was determined in conscious rabbits (n=5) using chronically implanted flowprobes. Resting blood flow was 8.3±0.6 ml/min and increased to 39.9±5.4 ml/min during high intensity exercise. Femoral arteries (n=12, 1705±43 μm outer diameter) harvested from a separate group of rabbits were mounted on cannulas and diameter was continuously monitored by video system. Functional integrity of the endothelium was tested with acetylcholine. The arteries were set at a transmural pressure of 100 mm Hg and preconstricted with phenylephrine to 73±3 % of initial diameter. Using a roller pump with pressure held constant, the arteries were perfused intraluminally with warmed, oxygenated Krebs' solution (pH=7.4) over a physiological range of flows up to 35 ml/min. As flow increased from 5 ml/min to 35 ml/min, diameter decreased significantly (p<0.05) from 1285±58 μm to 1100±49 μm. Thus, in vessels with a functional endothelium, increasing intraluminal flow over a physiological range of flows produced constriction, not dilation. Based on these results, it seems unlikely that flow-mediated vasodilation in the rabbit femoral artery contributes to exercise hyperemia., P. S. Clifford ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Wire myograph is a device for the in vitro investigation of both, active and passive properties of arteries. Arteries from a variety of animal species, pathological states, and vascular beds were investigated using this method. We focus on the normalization procedure which is aimed to standardize experimental settings and, in part, to simulate physiological conditions. During normalization, it is determined the internal circumference of a vessel stretched to a tension that corresponds to the transmural pressure of 100 mm Hg (IC100). Once it is determined, the internal circumference is traditionally set to (0.9 ⋅ IC100). However, this constant 0.9, called also the normalization factor (NF), was experimentally determined for rat small mesenteric arteries only. Therefore, the aim of our work was to show the influence of different NFs on the passive tension and reactivity of both, rat femoral arteries (FA) an d the first branches of superior mesenteric arteries (MA). We found out that the maximal active wall tension of the FA was achieved at the NF value of 1.1, and that of the MA at 0.9. Considering the values of the active wall tension we suggest that higher reactivity and better signal-to- noise ratio in FA can be achieved when the NF is set at least to 1.0., P. Slezák, I. Waczulíková, P. Bališ, A. Púzserová., and Obsahuje bibliografii
Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I K1 in arrhythmogenesis, this study was aimed at the effect of acetaldehyd e, the primary metabolite of ethanol, on I K1 in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I K1 with IC 50 = 53.7± 7.7 μM at -110 mV; a significant inhibition was documented even at clinically -relevant concentrations (at 3 μM by 13.1 ±3.0 % ). The inhibition was voltage -independent at physiological voltages above - 90 mV. The I K1 changes under acetaldehyde may contribute to alcohol - induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of a ldehyde dehydrogenase where the acetaldehyde level may be elevated., M. Bébarová, P. Matejovič, M. Šimurdová, J. Šimurda., and Obsahuje bibliografii
The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration., J. Šroubek, J. Hort, V. Komárek, M. Langmeier, G. Brožek., and Obsahuje bibliografii
Acrylamide (AA) is a highly reactive organic compound capable of polymerization to form polyacrylamide, which is commonly used throughout a variety of industries. Given its toxic effect on humans and animals, the last 20 years have seen an increased interest in research devoted to the AA. One of the main sources of AA is food. AA appears in heated food following the reaction between amino acids and reduced sugars. Large concentrations of AA can be found in popular staples such as coffee, bread or potato products. An average daily consumption of AA is between 0.3-2.0 μg/kg b.w. Inhalation of acrylamide is related with occupational exposure. AA delivered with food is metabolized in the liver by cytochrome P450. AA biotransformation and elimination result in formation of toxic glycidamide (GA). Both, AA and GA can be involved in the coupling reaction with the reduced glutathione (GSH) forming glutathione conjugates which are excreted with urine. Biotransformation of AA leads to the disturbance in the redox balance. Numerous research proved that AA and GA have significant influence on physiological functions including signal propagation in peripheral nerves, enzymatic and hormonal regulation, functions of muscles, reproduction etc. In addition AA and GA show neurotoxic, genotoxic and cancerogenic properties. In 1994, International Agency for Research on Cancer (IARC) classified acrylamide as a potentially carcinogenic substance to human., M. Semla, Z. Goc, M. Martiniaková, R. Omelka, G. Formicki., and Obsahuje bibliografii
Threshold intensities for epileptic phenomena induced by cortical stimulation were used for comparison of the action of GABA-B and GABA-A antagonists in rats with implanted electrodes. Both CGP 35348 (200 mg/kg i.p.) and bicuculline (4 mg/kg i.p.) significantly decreased thresholds for spike-and-wave afterdischarges and their motor counterpart (clonic seizures) whilst transition into the second, limbic type of afterdischarge as well as threshold for movements directly bound to stimulation remained uninfluenced by either drug., D. Živanović, K. Bernášková, Yu. Kaminskij, P. Mareš., and Obsahuje bibliografii
Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectomized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of DA antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and DA actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of DA through D2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of DA through D1 receptors and in other part by inhibition of stimulatory action of DA through D2 receptors., C. M. Leite, G. J. R. Machado, R. C. M. Dornelles, C. R. Franci., and Obsahuje bibliografii a bibliografické poznámky
The effects of lyotropic (swelling) anions (Cl-, Br-, NO3- and I-) on contractile properties of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were investigated in vitro at 20 °C and 35 °C. Isolated muscles bathed in anionic Tyrode solution were stimulated directly and isometric single twitches and fused tetanic contractions were recorded. In a Cl- Tyrode solution a decrease of the bathing temperature led to a cold potentiation of the twitch tension (Pt) in EDL muscles, however, to a cold depression in SOL muscles, in both muscles combined with a prolongation of contraction (CT) and half relaxation (HRT) times. The extent and order of the potentiating effect of lyotropic anions on the Pt, CT and HRT in EDL and SOL were quite similar and increased in the order: Cl-< Br- < NO3- < I-. Since the lyotropic anions did not influence tetanic tensions, the twitch-tetanus ratio (TTR) was increased in NO3- and I- solutions. All effects of the anions were rapidly and completely reversed in both muscles when the test solution was replaced by the normal one. The temperature decrease caused no significant alteration in the potentiation capacity of the anions or in the kinetics of their action and reversibility., Y. Wondmikun, T. Soukup, G. Asmussen., and Obsahuje bibliografii
Adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5’-N-methyluronamide (IB-MECA) has been tested from the point of view of potentiating the effects of hematopoietic growth factors interleukin-3 (IL-3), stem cell factor (SCF), granulocyte- macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) on the growth of hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) in suspension of normal mouse bone marrow cells in vitro. IB-MECA alone induced no GM-CFC growth. Significant elevation of numbers of GM-CFC evoked by the combinations of IB-MECA with IL-3, SCF, or GM-CSF as compared with these growth factors alone has been noted. Combinat ion of IB-MECA with G-CSF did not induce significantly higher numbers of GM-CFC in comparison with G-CSF alone. Joint action of three drugs, namely of IB-MECA + IL-3 + GM-CSF, produced significantly higher numbers of GM-CFC in comparison with the combinations of IB-MECA + IL-3, IB-MECA + GM-CSF, or IL-3 + GM-CSF. These results give evidence of a significant role of selective activation of adenosine A3 receptors in stimulation of the growth of granulocyte/macrophage hematopoietic progenitor cells., M. Hofer ... [et al.]., and Obsahuje seznam literatury
Ischemic preconditioning (IP) protects the heart against subsequent prolonged ischemia. Whether the β-adrenoceptor/adenylate cyclase pathway contributes to this cardioprotection is not yet fully known. Using enzyme catalytic cytochemistry we studied the adenylate cyclase activity and its distribution in the preconditioned rat heart. Adenylate cyclase activity was examined in Langendorff-perfused rat hearts subjected to the following conditions: control perfusion; 30 min regional ischemia; 5 min occlusion and 10 min reperfusion (IP); IP followed by ischemia. Ischemia-induced arrhythmias and the effect of ischemic preconditioning on the incidence of arrhythmias were analyzed. At the end of experiment the heart was shortly prefixed with glutaraldehyde. Tissue samples from the left ventricle were incubated in a medium containing the specific substate AMP-PNP for adenylate cyclase and then routinely processed for electron microscopy. Adenylate cyclase activity was cytochemically demonstrated in the sarcolemma and the junctional sarcoplasmic reliculum (JSR) in control hearts, while it was absent after test ischemia. The highest activity of the precipitate was observed after ischemic preconditioning. In the preconditioned hearts followed by test ischemia, adenylate cyclase activity in the precipitate was preserved in sarcolemma and even more in JSR. Protective effect of ischemic preconditioning was manifested by the suppression of severe arrhythmias. These rresults indicate the involvement of the adenylate cyclase system in mechanisms underlying ischemic preconditioning., Ľ. Okruhlicová, T. Ravingerová, D. Pancza, N. Tribulová, J. Styk, R. Štetka., and Obsahuje bibliografii
Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pyloriinfected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori., J. Astl, I. Šterzl., and Obsahuje bibliografii
Several deleterious effects may occur when intense and exhaustive exercise (IE) is not well-planned. This study aimed to investigate the effects of a short duration IE on body chemical composition and hypothalamic-pituitary-adrenal (HPA) axis. C57Bl/6 mice were distributed into four groups (10 mice per group): control (C-4D and C-10D), 4 days (E-4D), and 10 days of IE (E-10D). IE program consisted of a daily running session at 85 % of maximum speed until the animal reached exhaustion. Body weight as well as total body water, fat and protein content were determined from animal carcasses. HPA activation was assessed by plasma corticosterone levels measured by radioimmunoassay and the weight of both the adrenal glands and thymus were measured. Plasma corticosterone levels increased by 64 % in both the E-4D and E-10D groups. The weight of the adrenal glands augmented by 74 % and 45 %, at 4 and 10 days of IE, respectively, whereas thymus weight diminished by 15 % only in the E-10D group. The total carcass fat content decreased by 20 % only at 4 days IE, whereas protein content decreased by 20 % in both E-4D and E-10D groups. A relationship between corticosterone plasma levels and loss of body protein content in both E-4D and E-10D groups was observed (R2=0.999). We concluded that IE may be related to HPA axis activation associated with remodeling of body chemical composition in C57BL/6 mice., E. F. Rosa, G. A. Alves, J. Luz, S. M. A. Silva, D. Suchecki, J. B. Pesquero, J. Aboulafia, V. L. A. Nouailhetas., and Obsahuje bibliografii
Triiodothyronine administration before partial hepatectomy increased the activity of mitochondrial glycerophosphate cytochrome c reductase. The enzyme activity was further activated after partial hepatectomy during the regenerative process. Our findings showed that: a) the increase of glycerophosphate cytochrome c reductase induced by triiodothyronine was further potentiated by the regeneration process, b) the high activity of the glycerophosphate shuttle was maintained after partial hepatectomy during the period, when most of the liver tissue had again been recovered., H. Lotková, H. Rauchová, Z. Drahota., and Obsahuje bibliografii
Objectives of the study were to investigate impact of ischemic preconditioning (Ipre) and sulforaphane (SFN) and combination of them on nuclear factor 2 erythroid related factor 2 (Nrf2) gene and its dependent genes, heme oxygenase-1 (HO1) and NADPHquinone oxidoreductase1 (NQO-1) and inflammatory cytokines TNF-α, IL1β, and intercellular adhesion molecule-1 (ICAM1) and caspase-3 in renal ischemia/reperfusion (I/R) injury. Ninety male Sprague Dawely rats were classified into 5 groups (each consists of 18 rats): sham, control, Ipre, sulforaphane and Sulfo+Ipre. Each group was subdivided into 3 subgroups each containing 6 rats according to time of harvesting kidney and taking blood samples; 24 h, 48 h, and 7 days subgroups. Renal functions including serum creatinine, BUN were measured at basal conditions and by the end of experiment. Expression of Nrf2, HO-1, NQO-1, TNF-α, IL-1β, and ICAM-1 was measured by real time PCR in kidney tissues by the end of experiment. Also, immunohistochemical localization of caspase-3 and chemical assay of malondialdehyde (MDA), GSH and SOD activity were measured in kidney tissues. Both Ipre and SFN improved kidney functions, enhanced the expression of Nrf2, HO-1, and NQO-1, attenuated the expression of inflammatory (TNF-α, IL-1, and ICAM-1) and apoptotic (caspase-3) markers. However, the effect of sulforaphane was more powerful than Ipre. Also, a combination of them caused more improvement in antioxidant genes expression and more attenuation in inflammatory genes but not caspase-3 than each one did separately. Sulforaphane showed more powerful effect in renoprotection against I/R injury than Ipre as well as there might be a synergism between them at the molecular but not at the function level., A. A. Shokeir, N. Barakat, A. M. Hussein, A. Awadalla, A. M. Harraz, S. Khater, K. Hemmaid, A. I. Kamal., and Obsahuje bibliografii
Four groups of goldfish were exposed to cadmium in a concentration of 20 mg Cd/l water under aquarium conditions. The duration of exposure was 1, 4, 7 and 15 days. It was shown that the activity of superoxide dismutase (SOD) in the red blood cells (RBC) significantly decreased after the first day of cadmium exposure. However, the SOD activity increased after 7 and 15 days of cadmium treatment. Elevated activity of catalase (CAT) was found in erythrocytes of cadmium-treated fishes after 15 days, whereas plasma GOT levels was increased after 7 and 15 days and GPT levels after 1, 4, 7 and 15 days of cadmium treatment. This was accompanied by a significant decrease of blood hemoglobin concentrations (after 15 days) and hematocrit values (after 7 and 15 days). However, the concentration of blood glucose significantly increased after 1, 4, 7 and 15 days of cadmium exposure. These results indicate that cadmium causes oxidative stress and tissue damage in the exposed fishes., R.V. Žikić, A. Š. Štajn, S. Z. Pavlović, B. I. Ognjanović, Z. S. Saičić., and Obsahuje bibliografii
Paraoxonase 1 (PON1) seems to have a relevant role in detoxifying processes and in atherosclerosis. The aim of this study was to determine PON1 activity, the total antioxidant capacity, as well as entire lipid profile in children for screening of possible risk of atherosclerosis development. Serum PON1 arylesterase/paraoxonase activities were determined spectrophotometrically. The total antioxidant capacity of the serum was measured by TEAC method. Parameters of lipid profile were analyzed by routine laboratory methods. It has been shown that PON1 arylesterase/ paraoxonase activities were very similar to values found in adults. In children, no significant correlation between PON1 arylesterase activity and HDL was observed. PON1 paraoxonase activity correlated only with atherogenic index. PON1 arylesterase activity was significantly higher in girls than in boys. The antioxidant capacity was inversely related to the body mass index. In this study, PON1 activity was determined in healthy children aged 11 to 12 years and we found a similarity in PON1 activities of children and adults. Moreover, the results of our study support the hypothesis that higher body weight of children may contribute to a greater risk for development of atherosclerosis in which oxidative stress plays a role., K. Sumegová, Z. Nagyová, I. Waczulíková, I. Žitňanová, Z. Ďuračková., and Obsahuje bibliografii a bibliografické odkazy
We studied the temporal relationships and the patterns of electromyographic activities of the posterior cricoarytenoid and thyreoarytenoid muscles (laryngeal abductor and adductor), the diaphragm and abdominal muscles in anesthetized cats during mechanically induced tracheobronchial and laryngopharyngeal coughs, expiration and aspiration reflexes. The posterior cricoarytenoid muscle activity reached the maxima just before the peak of diaphragmatic activity in both types of cough and aspiration reflexes and slightly before the top of abdominal muscle activity in coughs and the expiration reflex. Thus, this muscle contributes to the inspiratory phase of coughs and aspiration reflex and also to the expulsive phase of coughs and the expiration reflex. The thyreoarytenoid muscle presented strong discharges in the compressive phase of coughs and expiration reflex (during the rising part of the abdominal muscle activity) and in the subsequent laryngoconstriction (following the diaphragmal and/or abdominal muscle activity) in all four reflexes. This muscle was also slightly activated at the beginning of the aspiration reflex. The existence of four phases of the cough reflex is also discussed., I. Poliaček, A. Stránsky, J. Jakuš, H. Baráni, Z. Tomori, E. Halašová., and Obsahuje bibliografii
Recovery from exercise refers to the period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It is a dynamic period in which many physiological changes occur. A large amount of research has evaluated the effect of training on intramuscular lipid metabolism. However, data are limited regarding intramuscular lipid metabolism during the recovery period. In this study, lipid metabolism-related proteins were examined after a single bout of exercise in a time-dependent way to explore the mechanism of how exercise induces intramuscular lipid metabolism adaptation. Firstly, all rats in the exercise group underwent a five-week training protocol (HIIT, five times/week), and then performed a more intense HIIT session after 72 h of the last-time five-week training. After that, rats were sampled in a time-dependent way, including 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h following the acute training session. Our results discovered that five weeks of HIIT increased the content of intramuscular triglyceride (IMTG) and enhanced the lipolytic and lipogenesis-related proteins in skeletal muscle. Furthermore, IMTG content decreased immediately post HIIT and gradually increased to baseline levels 48 h postexercise, continuing to over-recover up to 96 h postexercise. Following acute exercise, lipolytic-related proteins showed an initial increase (6-12 h) before decreasing during recovery. Conversely, lipogenesis-related proteins decreased following exercise (6-12 h), then increased in the recovery period. Based on the changes, we speculate that skeletal muscle is predominated by lipid oxidative at the first 12 h postexercise. After this period, lipid synthesis-related proteins increased, which may be the result of body recovery. Together, these results may provide insight into how the lipid metabolism-related signaling changes after chronic and acute HIIT and how protein levels lipid metabolism correlates to IMTG recovery., Min Chen, Lei Zhou, Siyu Chen, Ruonan Shangguan, Yaqian Qu, Jingquan Sun., and Obsahuje bibliografii
The biosynthesis and metabolism of testosterone and cortisol are altered by the high levels of adipose tissue and the constant state of low-grade inflammation of obesity. Resistance exercise (REx) has become one of the main lifestyle interventions prescribed to obese individuals due to its ability to positively influence body composition and some biomarkers, such as cholesterol and insulin resistance. Yet, little research has been done in obese examining the effects of REx on the testosterone and blood cortisol responses, two integral hormones in both exercise and obesity. The obese testosterone response to REx and whether or not it is blunted compared to lean individuals remains elusive. Conflicting findings concerning the blood cortisol response have also been reported, likely due to variance in REx protocol and the level of obesity in the participants in studies. Comparatively, both of these hormones have been extremely well studied in untrained lean males, which could be used as a basis for future research in obese males. However, without this endocrinological information, it is unknown if the current acute REx prescriptions are appropriate for eliciting a favorable acute endocrinological response, and ultimately, a positive chronic adaptation in obese males., C. B. O'Leary, A: C. Hackney., and Obsahuje bibliografii
Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudilinduced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NOdependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats., A. Brunová, M. Bencze, M. Behuliak, J. Zicha., and Obsahuje bibliografii
Natural glucocorticoid hydrocortisone was suggested as a potent substitution for dexamethasone in the treatment of bronchopulmonary dysplasia in neonates. The aim of this study was to investigate whether hydrocortisone is able to affect the expression of apoptotic genes and the intensity of naturally occurring cell death in the developing rat hippocampus. Hormone treatment decreased procaspase-3 and active caspase-3 levels as well as DNA fragmentation intensity in the hippocampal formation of one-week-old rats in 6 h after injection. These changes were accompanied by an upregulation of antiapoptotic protein Bcl-XL, while expression of proapoptotic protein Bax remained unchanged. The action of hydrocortisone was glucocorticoid receptor-independent, as the selective glucocorticoid receptor agonist dexamethasone did not affect either apoptotic protein levels or DNA fragmentation intensity in the hippocampal region. The data are the first evidences for in vivo antiapoptotic effects of hydrocortisone in the developing hippocampus., P. N. Menshanov, ... [et al.]., and Obsahuje seznam literatury
Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions., M.A. Fahim ... [et al.]., and Obsahuje seznam literatury
Parallel glucose measurements in blood and other different tissues give us knowledge about dynamics of glycemia changes, which depend on vascularization, distribution space and local utilization by tissues. Such information is important for the understanding of glucose homeostasis and regulation. The aim of our study was to determine the time-lag between blood, brain, and adipose tissue during rapid glucose changes in a male hHTG rat (n=15). The CGMS sensor Guardian RT (Minimed/Medtronic, USA) was inserted into the brain and into the abdominal subcutaneous tissue. Fixed insulin and variable rate of glucose infusion was used to maintain euglycemia during sensor calibration period. At 0 min, 0.5 g/kg of bolus of glucose was administered, and at 50 min, 5 IU/kg of bolus of insulin was administered. Further glucose and insulin infusion was stopped at this time. The experiment was finished at 130 min and animals were euthanized. The time-shift between glycemia changes in blood, brain, and subcutaneous tissue was calculated by identification of the ideal correlation function. Moreover, the time to achieve 90 % of the maximum glucose excursion after intervention (T90) was measured to compare our data with the literature. The time-lag blood vs. brain and blood vs. subcutaneous tissue was 10 (10; 15) min and 15 (15; 25) min, respectively. The difference was statistically significant (P=0.01). T90 after glucose bolus in brain and subcutaneous tissue was 10 min (8.75; 15) and 15 min (13.75; 21.25), respectively. T90 after insulin bolus in brain and subcutaneous tissue was 10 min (10; 15) and 20 min (20; 27.5), respectively. To the contrary, with literature, our results showed earlier glucose level changes in brain in comparison with subcutaneous tissue after glucose and insulin boluses. Our results suggest that glucose dynamics is different within monitored tissues under rapid changing glucose level and we can expect similar behavior in humans. Improved knowledge about glucose distribution and dynamics is important for avoiding hypoglycemia., M. Žourek, P. Kyselová, D. Čechurová, Z. Rušavý., and Seznam literatury
Acute liver failure (ALF) is a clinical condition with very high mortality rate. Its pathophysiological background is still poorly understood, which necessitates a search for optimal experimental ALF models with features resembling those of the human disorder. Taking into consideration reproducibility of induction of ALF, adequate animal size, cost of animals, the required time gap between insult and death of animals (“therapeutic window”), potential risk to investigator and other aspects, administration of thioacetamide (TAA) in rats is currently most recommended. However, the fundamental details of this ALF model have not yet been evaluated. This prompted us to investigate, first, the course of ALF as induced by intraperitoneal TAA at doses increasing from 175 to 700 mg/kg BW per day. The animals’ survival rate, plasma alanine and aspartate aminotransferase activities, and bilirubin and ammonia levels were determined over the follow-up period. Second, we examined whether Wistar and Lewis rats exhibit any differences in the course of ALF induced by different TAA doses. We found that the optimal dose for ALF induction in rats is 350 mg.kg-1 i.p., given as a single injection. Wistar rats proved more susceptible to the development of TAA-induced ALF compared with Lewis rats. Collectively, our present findings provide a sound methodological background for experimental studies aimed at evaluation of pathophysiology and development of new approaches in the therapy of ALF., E. Koblihová, I. Mrázová, Z. Vernerová, M. Ryska., and Obsahuje bibliografii
We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias., M. Fialová, K. Dlugošová, L. Okrouhlicová, F. Kristek, M. Manoach, N. Tribulová., and Obsahuje bibliografii a biblioigrafické údaje
Four mouse bone marrow or thymus cell populations, namely granulopoietic/monocytopoietic, erythropoietic, B-lymphopoietic, and T-lymphopoietic precursor cells have been assayed by RTPCR technique for the presence and relative amounts of adenosine A1, A2a, A2b, and A3 receptor mRNA. It has been found that (i) all four populations studied express all four adenosine receptor subtypes, (ii) the A1 receptor is the least expressed in all populations studied, (iii) the A3 receptor is markedly expressed in the populations of granulopoietic/monocytopoietic and erythropoietic cells, (iv) the A2a receptor is markedly expressed in the populations of B-lymphopoietic and T-lymphopoietic cells, and v) the A2b receptor does not predominate in any of the precursor cells studied. Our data offer a new possibility for the assessment of the readiness of these cells to respond, by receptor-mediated mechanisms, to adenosine or its analogs present in the tissues as a result of endogenous processes and/or following their administration., D. Štreitová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Expression of mRNA for adenosine receptor subtypes A1, A2a, A2b, and A3 in normal and lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages has been investigated using the method of quantitative real-time polymerase chain reaction. The results have shown a very low, unquantifiable expression of adenosine A1 receptor mRNA in both normal and LPS-activated macrophages. The other three adenosine receptor mRNAs have been found to be expressed at various but always quantifiable levels. Activation of the macrophages by LPS induced upregulation of the expression of adenosine receptor A2a and A2b mRNA, whereas the expression of adenosine receptor A3 mRNA was downregulated. Unstimulated macrophages exhibited a high expression of the A2b adenosine receptor mRNA. The findings are discussed from the point of view of the antiinflammatory and hematopoiesis-stimulating roles of the adenosine receptor signaling., D. Štreitová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
This review briefly outlines the history and possibilities of bone reconstruction using various types of artificial materials, which allow interaction with cells only on the surface of the implant or enable ingrowth of cells inside the material. Information is also provided on the most important properties of bone cells taking part in bone tissue development, and on diseases and regeneration. The most common cell types used for testing cell-material interaction in vitro are listed, and the most commonly used approaches to this testing are also mentioned. A considerable part of this review is dedicated to the physical and chemical properties of the materi al surface, which are decisive for the cell-material interaction, and also to modifications to the surface of the material aimed at integrating it better with the surrounding bone tissue. Special attention is paid to the effects of nanoscale and microscale surface roughness on cell behaviour, to material surface patterning, which allows regionally-selective adhesion and growth of cells, an d also to the surface chemistry. In addition, coating the materials with bioactive layers is examined, particularly those create d by deposition of fullerenes, hybrid metal-fullerene composites, carbon nanotubes, nanocrystalline diamond films, diamond-like carbon, and nanocomposite hydrocarbon plasma polymer films enriched with metals., M. Vandrovcová, L. Bačáková., and Obsahuje bibliografii a bibliografické odkazy
Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro . After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western blot. It was suggested that APN promoted the optical density (OD) value of VEPCs, enhanced mRNA expression of Bcl-2 and VEGF, and inhibited cell apoptotic rate. Furthermore, protein expression of pSTAT3 was also increased in the presence of APN. Moreover, APN changed-proliferation, apoptosis and VEGF expression of VEPCs were partially suppressed after blocking the mTOR-STAT3 signaling pathway by the mTOR inhibitor XL388. It was indicated that APN promoted biological functions of VEPCs through targeting the mTOR-STAT3 signaling pathway., Xiaoying Dong, Xia Yan, Wei Zhang, Shengqiu Tang., and Obsahuje bibliografii
Adiponectin acts as an endogenous antithrombotic factor. However, the mechanisms underlying the inhibition of platelet aggregation by adiponectin still remain elusive. The present study was designed to test whether adiponectin inhibits platelet aggregation by attenuation of oxidative/nitrative stress. Adult rats were fed a regular or high-fat diet for 14 weeks. The platelet was immediately separated and stimulated with recombinant full-length adiponectin (rAPN) or not. The platelet aggregation, nitric oxide (NO) and superoxide production, endothelial nitric oxide synthase (eNOS)/inducible NOS (iNOS) expression, and antioxidant capacity were determined. Treatment with rAPN inhibited hyperlipidemia- induced platelet aggregation (P<0.05). Interestingly, total NO, a crucial molecule depressing platelet aggregation and thrombus formation , was significantly reduced, rather than increased in rAPN-treated platelets. Treatment with rAPN markedly decreased superoxide production (-62 %, P<0.05) and enhanced antioxidant capacity (+38 %, P<0.05) in hyperlipidemic platelets. Hyperlipidemia-induced reduced eNOS phosphorylation and increased iNOS expression were significantly reversed following rAPN treatment (P<0.05, P<0.01, respectively). Taken together, these data suggest that adiponectin is an adipokine that suppresses platelet aggregation by enhancing eNOS activation and attenuating oxidative/nitrative stress including blocking iNOS expression and superoxide production., W.-Q. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Adiponectin is an adipokine increasing glucose and fatty acid metabolism and improving insulin sensitivity. The aim of this study was to investigate the role of adiponectin in the regulation of adipocyte lipolysis. Human adipocytes isolated from biopsies obtained during surgical operations from 16 non-obese and 17 obese subjects were incubated with 1) human adiponectin (20 μg/ml) or 2) 0.5 mM AICAR - activator of AMPK (adenosine monophosphate activated protein kinase). Following these incubations, isoprenaline was added (10-6 M) to investigate the influence of adiponectin and AICAR on catecholamine-induced lipolysis. Glycerol concentration was measured as lipolysis marker. We observed that adiponectin suppressed spontaneous lipolysis by 21 % and isoprenaline-induced lipolysis by 14 % in non-obese subjects. These effects were not detectable in obese individuals, but statistically significant differences in the effect of adiponectin between ob ese and non-obese were not revealed by two way ANOVA test. The inhibitory effect of AICAR and adiponectin on lipolysis was reversed by Compound C. Our results suggest, that adiponectin in physiological concentrations inhibits spontaneous as well as catecholamine-induced lipolysis. This effect might be lower in obese individuals and this regulation seems to involve AMPK., Z. Wedellová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
High -energy intake which exceeds energy expenditure leads to the accumulation of triglycerides in adipose tissue, predominantly in large -size adipocytes. This metabolic shift, which drives the liver to produce atherogenic dyslipidemia, is well documented. In addition, an increasing amount of monocytes/macrophages, predominantly the proinflammatory M1- type, cumulates in ectopic adipose tissue. The mechanism of this process, the turnover of macrophages in adipose tissue and their direct atherogenic effects all remain to be analyzed., R. Poledne, I. Králová Lesná, S. Čejková., and Obsahuje bibliografii
We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs., L. Xu, Y. Liu., and Obsahuje seznam literatury
The function of adult neurogenesis in the dentate gyrus is not yet completely understood, though many competing theories have attempted to explain the function of these newly -generated neurons. Most theories give adult neurogenesis a role in aiding known hippocampal/dentate gyrus functions. Other theories offer a novel role for these new cells based on their unique physiological qualities, such as their low excitability threshold. Many behavioral tests have been used to test these theories, but results have been inconsistent and often contradictory. Substantial variability in tests and protocols may be at least partially responsible for the mixed results. On the other hand, conflicting results arising from the same tests can serve as aids in elucidating the function of adult neurogenesis. Here, we offer a hypothesis that considers the cognitive nature of tasks commonly used to assess the function of adult neurogenesis, and introduce a dichotomy between tasks focused on discrimination vs. generalization. We view these two aspects as opposite ends of the continuous spectrum onto which traditional tests can be mapped. We propose that high neurogenesis favors behavioral discrimination while low adult neurogenesis favors behavioral generalization of a knowledge or rule. Since many tasks require both, the effects of neurogenesis could be cancelled out in many cases. Although speculative, we hope that our view presents an interesting and testable hypothesis of the effect of adult neurogenesis in traditional behavioral tasks. We conclude that new, carefully designed behavioral tests may be necessary to reach a final consensus on the role of adult neurogenesis in behavior., A. Pistikova, H. Brozka, A. Stuchlik., and Obsahuje bibliografii
Advanced glycation end products (AGEs) may play an important adverse role in process of atherosclerosis, diabetes, aging and chronic renal failure. Levels of Ne-carboxymethyllysine and fluorescent AGE values were estimated in two nutritional population groups - alternative group (vegetarians - plant food, milk products, eggs) and traditional group (omnivorous subjects). Vegetarians have a significantly higher carboxymethyllysine content in plasma and fluorescent AGE values. Intake of proteins, lysine and monosaccharides as well as culinary treatment, consumption of food AGEs (mainly from technologically processed products) and the routes of Maillard reaction in organism are the substantial sources of plasma AGEs. Vegetarians consume less proteins and saccharides. Lysine intake is significantly reduced (low content in plant proteins). Subjects on alternative nutrition do not use high temperature for culinary treatment and consume low amount of technologically processed food. Fructation induced AGE fluorescence is greater as compared with that induced by glucose. It is due to higher participation of a more reactive acyclic form of fructose. Intake of vegetables and fruit with predominance of fructose is significantly higher in vegetarians. Comparison of nutrition and plasma AGEs in vegetarian and omnivorous groups shows that the higher intake of fructose in alternative nutrition of healthy subjects may cause an increase of AGE levels., M. Krajčovičová-Kudláčková, K. Šebeková, R. Schinzel., and Obsahuje bibliografii
The slowly metabolized proteins of the extracellular matrix, typically collagen and elastin, accumulate reactive metabolites through uncontrolled non-enzymatic reactions such as glycation or the products arising from the reaction of unsaturated long chain fatty acid metabolites (possessing aldehydic groups). A typical example of these non-enzymatic changes is the formation of advanced glycation end-products (AGEs), resulting from the reaction of carbohydrates with the free amino group of proteins. The accumulation of AGEs and the resulting structural alterations cause altered tissue properties (increased stiffness, reduced elasticity) that contribute to their reduced catabolism and to their aging. Posttranslational nonenzymatic modifications of the proteins of the extracellular matrix (the formation of a typical AGE product - pentosidine) were studied in three types of tissue of three rat strains subjected to a high-fructose diet. Chronic (three-week) hyperglycemia (resulting from fructose loading) caused a significant increase in pentosidine concentration mainly in the aorta and skin of the three rat strains (Lewis, Wistar and hereditary hypertriglyceridemic rats)., K. Mikulíková, A. Eckhardt, J. Kuneš, J. Zicha, I. Mikšík., and Obsahuje bibliografii a bibliografické odkazy
Advanced glycation end-product (AGE) pentosidine has previously been demonstrated in different tissues and body fluids. It was suggested as a novel marker for evaluating the pathologic activity in rheumatoid arthritis (RA). In this study we analyzed the relation between pentosidine and markers of inflammation, cartilage turnover, immune response, and disease status of RA. Using HPLC, we analyzed pentosidine in serum and synovial fluid from 39 patients with RA and in serum from 38 healthy controls. Cartilage oligomeric matrix protein (COMP) and antibodies to CCP (anti-CCP) were measured by ELISA. Clinical disease status was assessed by Disease Activity Score 28 (DAS 28) and functional status by Health Assessment Questionnaire (HAQ). We demonstrated significantly higher serum levels of pentosidine in RA patients in comparison with controls. Pentosidine in serum significantly correlated with pentosidine in synovial fluid. Serum pentosidine levels were associated with erythrocyte sedimentation rate (p<0.03) but not with CRP, COMP, anti-CCP antibodies, DAS 28, or HAQ. In contrast to previous studies, we could not show any correlation of pentosidine levels with inflammatory status, clinical disease activity, markers of immune response, or cartilage breakdown. However, AGEs can be suggested as important players participating in joint destruction rather than markers of disease activity., L. Šenolt, M. Braun, J. Vencovský, L. Šedová, K. Pavelka., and Obsahuje bibliografii a bibliografické odkazy
Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11±1.15x103 AU/g vs controls 4.08±0.71x103 AU/g, p<0.001, vs DM1 4.14±0.86x103 AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50±75.15 mmol/l vs healthy subjects 79.80±23.72 mmol/l, p<0.001, vs DM1 97.50±30.91 mmol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products., M. Kalousová, J. Škrha, T. Zima., and Obsahuje bibliografii
It has been shown that besides positron emission tomography, single photon emission computed tomography and magnetic resonance imaging; contrast echocardiography can be used for qualitative and quantitative myocardial perfusion assessment. In this review, the properties of ultrasound contrast agents, imaging techniques and acquisition methods are shortly described and the possibilities of perfusion echocardiography are summarized. The main focus is put on the description of three perfusion models: mathematical models, physical models assuming an ideal inflow and physical models including inflow measurement., R. Kolář ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
AMP -activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α 2-subunit deletion affects heart function and ische mic tolerance of adult and aged mice. AMPK α 2 -/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α 2-subunit protein level, but no difference in AMPK α 1-subunit was detected between the strains. Both α 1- and α 2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α 2-subunit deletion and high-fat feeding on heart function and myocardia l ischemic tolerance in aged female mice are not additive., K. Slámová, F. Papoušek, P. Janovská, J. Kopecký, F. Kolář., and Obsahuje bibliografii
Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca2+-activated K+ (BKCa) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR). Age-matched Wistar-Kyoto rats (WKYs) were used as normotensive controls. Exercise groups completed an 8-week exercise program. Elevation of the α and β1 proteins was unequal in MA myocytes from SHRs, with the β1 subunit increasing more than the α subunit. BKCa contribution to vascular tone regulation was higher in the myocytes and arteries of SHRs compared to WKYs. SHR BKCa channel subunit protein expression, β1/α ratio, whole cell current density and single-channel open probability was also increased compared with WKYs. Aerobic exercise lowered systemic blood pressure and normalized hypertension-associated BKCa alterations to normotensive control levels in the SHRs. These effects were more pronounced in the moderate-intensity group than in the low-intensity group. There is a dose-effect for aerobic exercise training in the range of low to moderate-intensity and accompanying volume for the correction of the pathological adaptation of BKCa channels in myocytes of MAs from SHR., Y. Zhang, Y. Chen, L. Zhang, N. Lu, L. Shi., and Obsahuje bibliografii
Postconditioning (PostC) is a re cently discovered phenomenon whereby brief repetitive cycles of ischaemia with intermittent reperfusion following prolonged is chaemia elicit cardioprotection. This study investigated whether the age, genetic characteristics or number of repetitive cycles influenced the protective effect of PostC in mice. C57BL/6 floxed or non-floxed STAT-3 mice aged between 14-16 weeks (young) or 18-20 weeks (older) were perfused on a Langendorff apparatus and subjected to 35 min global ischaemia and 45 min reperfusion. PostC was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10s ischaemia and 10 s reperfusion. PostC-3 and PostC-6 in both young and older non-floxed mice reduced the myocar dial infarct size. In contrast, only PostC-3 reduced myocardial infarct size in young floxed mice. Neither PostC-3 nor PostC-6 reduced the in farct in older floxed mice. Our data reveal that genetic characteristics, a minute difference in age or the nu mber of postconditioning cycles are critical factors to be consid ered for the successful effect of ischaemic postconditioning in a murine model. Moreover, these factors should be taken into consideration for future experimental research or clinical applications of this protective phenomenon., S. J. Somers ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentyl enetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dose-specific suppression of the tonic phase needs further analysis. and Obsahuje seznam literatury
Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that agerelated alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation., E. Babušíková ... [et al.]., and Obsahuje seznam literatury
Age-associated changes in large blood vessels were characterized by increased arterial wall thickness, luminal dilation and impaired endothelial function. But little is known about the effect of age on structural and functional changes in small resistance arteries. The mechanisms underlying age-associated endothelial dysfunction in rat mesenteric resistance arteries were investigated in the present study. Small rat mesenteric arteries were excised and cannulated, and vascular endothelial functions were tested by acetylcholine (ACh). Our experiments showed (1) endotheliumdependent vasorelaxation induced by ACh was reduced in aged mesenteric arteries; (2) blockade of Kca channels markedly reduced the vasodilation in young and adult rats, the resultant reduction in aged rats was much smaller compared with young and adult rats; (3) inhibition of endothelial nitric oxide synthase (NOS) resulted in a significant reduction of vasodilation in young and adult, but there was a smaller reduction in aged rats. The results suggest that (1) endothelial function was impaired in mesenteric arteries of aged rats; (2) both Kca channels and nitric oxide (NO) contribute together to the ACh-induced vasorelaxation in small mesenteric arteries, and (3) both the impairment of Kca channel function and decreased NO account for the age-related endothelial dysfunction., E. Zhou, D. Qing, J. Li., and Obsahuje bibliografii a bibliografické odkazy
Processes of adult neurogenesis can be influenced by environmental factors. Here, we investigated the effect of microwave radiation (MWR) on proliferation and cell dying in the rat rostral migratory stream (RMS) - a migration route for the neuroblasts of the subventricular zone. Adult and juvenile (two weeks old) rats were exposed to a pulsed-wave MWR at the frequency of 2.45 GHz for 1 or 3 h daily during 3 weeks. Adult rats were divided into two groups: without survival and with two weeks survival after irradiation. Juvenile rats survived till adulthood, when were tested in the light/dark test. Proliferating cells in the RMS were labeled by Ki-67; dying cells were visualized by Fluoro-Jade C histochemistry. In both groups of rats irradiated as adults we have observed significant decrease of the number of dividing cells within the RMS. Exposure of juvenile rats to MWR induced only slight decrease in proliferation, however, it strikingly affected cell death even two months following irradiation. In addition, these rats displayed locomotor hyperactivity and decreased risk assessment in adulthood. Our results suggest that the long-lasting influence of radiation is manifested by affected cell survival and changes in animals´ behavior., A. Raček, K. Beňová, P. Arnoul, M. Závodská, A. Angelidis, V. Cigánková, V. Šimaiová, E. Račeková., and Obsahuje bibliografii
The growth of the prostate gland is androgen-dependent. Testosterone is converted to the most potent dihydrotestosterone (DHT) by 5α-reductase within the prostate. Androgen interacts with androgen receptors (AR) to regulate normal growth of the prostate and has also been implicated in both the progression of benign prostate hyperplasia and prostate cancer. This study was conducted to compare the mRNA expression of AR and 5α-reductase by the prostate gland from three age categories: immature, young-mature and old dogs. Quantitative gene expression was assessed by the real-time PCR and the results were expressed as a relative mRNA expression of the target gene. This study revealed that there was no significant difference in the mRNA expression of the AR gene by the prostate gland of immature, young and old dogs. In contrast, there is a highly significant (P<0.001) down-regulation in 5α-reductase gene by the prostate of young and old dogs as compared with immature dogs. However, there is no significant difference in mRNA expression of the 5α-reductase gene by the prostate gland from young and old dogs. This differential expression of AR and 5α-reductase genes, which are involved in the regulation of androgen effect on prostate gland, might reflect an age-dependent growth requirement of the gland for androgens., F. Shidaifat., and Obsahuje seznam literatury
a1_Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension – salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of reninangiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the saltsensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake., a2_On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals., J. Zicha, ... [et al.]., and Obsahuje seznam literatury
The aim of the study was to investigate age-related changes in postural responses to platform translation with 3 various velocities. We focused on the influence of linear velocity using the smoothed profile of platform acceleration (till 100 cm.s−2 ). Eleven healthy young (20-31 years) and eleven healthy elderly (65-76 years) subjects were examined. The subjects stood on the force platform with their eyes closed. Each trial (lasting for 8 sec) with different velocity (10, 15, 20 cm.s−1 ) of 20 cm backward platform translation was repeated 4 times. We have recorded displacements of the centre of pressure (CoP) and the EMG activity of gastrocnemius muscle (GS) and tibialis anterior muscle (TA). The results showed increased maximal values of CoP responses to the platform translation. There was also observed a scaling delay of CoP responses to platform translation with different velocities in elderly. The EMG activity of GS muscle during backward platform translation was of about similar shape in both groups during the slowest platform velocity, but it increased depending on rising velocity. EMG activity of TA was not related to the platform velocity. Early parts of postural responses showed significant co-activation of TA and GS muscles of elderly. It is likely that elderly increased body stiffening in order to help their further balance control., Z. Halická ... [et al.]., and Obsahuje seznam literatury
Certain aspects of balance control change with age, resulting in a slight postural instability. We examined healthy subjects between 20-82 years of age during the quiet stance under static conditions: at stance on a firm surface and/or on a compliant surface with eyes either open or closed. Body sway was evaluated from centre of foot pressure (CoP) positions during a 50 sec interval. The seven CoP parameters were evaluated to assess quiet stance and were analyzed in three age groups: juniors, middle-aged and seniors. The regression analysis showed evident increase of body sway over 60 years of age. We found that CoP parameters were significantly different when comparing juniors and seniors in all static conditions. The most sensitive view on postural steadiness during quiet stance was provided by CoP amplitude and velocity in AP direction and root mean square (RMS) of statokinesigram. New physiological ranges of RMS parameter in each condition for each age group of healthy subjects were determined. Our results showed that CoP data from force platform in quiet stance may indicate small balance impairment due to age. The determined physiological ranges of RMS will be useful for better distinguishing between small postural instability due to aging in contrast to pathological processes in the human postural control., D. Abrahamová, F. Hlavačka., and Obsahuje bibliografii a bibliografické odkazy
Vascular aging is associated with both structural and functional changes that can take place at the level of the endothelium, vascular smooth muscle cells and the extracellular matrix of blood vessels. With regard to the endothelium, reduced vasodilatation in response to agonists occurs in large conduit arteries as well as in resistance arteries with aging. Reviews concerning the different hypotheses that may account for this endothelial dysfunction have pointed out alterations in the equilibrium between endothelium-derived relaxing and constricting factors. Thus, a decreased vasorelaxation due to nitric oxide and, in some arteries, endothelium-derived hyperpolarizing factor as well as an increased vasoconstriction mediated by cyclooxygenase products such as thromboxane A2 are likely to occur in age-induced impairment of endothelial vasodilatation. Furthermore, enhanced oxidative stress plays a critical role in the deleterious effect of aging on the endothelium by means of nitric oxide breakdown due to reactive oxygen species. The relative contribution of the above phenomenon in age-related endothelial dysfunction is highly dependent on the species and type of vascular bed., R. L. Matz, C. Schott, J. C. Stoclet, R. Andriantsitohaina., and Obsahuje bibliografii
Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts., V. Nagibin, T. Egan Benova, C. Viczenczova, B. Szeiffova Bacova, I. Dovinova, M. Barancik, N. Tribulova., and Obsahuje bibliografii
Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In particular, we focused on the changes associated with aging, especially the role of small molecules, their role in physiological and pathophysiological processes and potential treatment options. Our previously published results and data from other authors lead to the conclusion that these unwanted changes are mainly linked to the hypothalamic-pituitary-adrenal axis can be slowed down, stopped, or in some cases even reversed by an appropriate treatment, but especially by a life-management adjustment., Martin Hill, Zdeněk Třískala, Pavla Honců, Milada Krejčí, Jiří Kajzar, Marie Bičíková, Leona Ondřejíková, Dobroslava Jandová, Ivan Sterzl., and Obsahuje bibliografii
Chronic airflow limitation, caused by chronic obstructive pulmonary disease (COPD) or by asthma, is believed to change the shape and the position of the diaphragm due to an increase in lung volume. We have made a comparison of magnetic resonance imaging (MRI) of diaphragm in supine position with pulmonary functions, respiratory muscle function and exercise tolerance. We have studied the differences between patients with COPD, patients with asthma, and healthy subjects. Most interestingly we found the lung hyperinflation leads to the changes in diaphragmatic excursions during the breathing cycle, seen in the differences between the maxim al expiratory diaphragm position (DPex) in patients with COPD and control group (p=0.0016) . The magnitude of the diaphragmatic dysfunction was significantly related to the airflow limitation expressed by the ratio of forced expiratory volume in 1 s to slow vital capacity (FEV 1 /SVC) , (%, p=0.0007); to the lung hyperinflation expressed as the ratio of the residual volume to total lung capacity (RV/TLC), (%, p=0.0018) and the extent of tidal volume constrain expressed as maximal tidal volume (V Tmax ), ([l], p=0 .0002); and the ratio of tidal volume to slow vital capacity (VT/SVC), (p=0.0038) during submaximal exercise. These results suggest that diaphragmatic movement fails to contribute sufficiently to the change in lung volume in emphysema. Tests of respiratory muscle function were related to the position of the diaphragm in deep expiration, e.g. neuromuscular coupling (P 0.1 /VT) (p=0.0232). The results have shown that the lung volumes determine the position of the diaphragm and function of the respiratory muscles. Chronic airflow limitation seems to change the position of the diaphragm, which thereafter influences inspiratory muscle function and exercise tolerance. There is an apparent relationship between the position of the diaphragm and the pulmonary functions and exercise tolerance., L. Hellebrandová, J. Chlumský, P. Vostatek, D. Novák, Z. Rýznarová, V. Bunc., and Obsahuje bibliografii
Because greater Akt substrate of 160 kDa (AS160) phosphorylation has been reported in insulin-stimulated skeletal muscles without improved Akt activation several hours post-exercise, we hypothesized that prior exercise would result in attenuated AS160 dephosphorylation in insulin-stimulated rat skeletal muscle. Epitrochlearis muscles were isolated from rats that were sedentary (SED) or exercised 3 h earlier (3 h postexercise; 3hPEX). Paired muscles were incubated with [3H]-2-deoxyglucose (2-DG) without insulin or with insulin. Lysates from other insulin-stimulated muscles from SED or 3hPEX rats were evaluated using AS160Thr642 and AS160Ser588 dephosphorylation assays. Prior exercise led to greater 2-DG uptake concomitant with greater AS160Thr642 phosphorylation and a non-significant trend (P=0.087) for greater AS160Ser588. Prior exercise also reduced AS160Thr642 and AS160Ser588 dephosphorylation rates. These results support the idea that attenuated AS160 dephosphorylation may favor greater AS160 phosphorylation post-exercise., E. B. Arias, H. Wang, G. D. Cartee., and Seznam literatury
Considerable evidence demonstrates that phenotypic switching of vascular smooth muscle cells (VSMCs) is influenced by aging and hypertension. During phenotypic switching, VSMCs undergo a switch to a proliferative and migratory phenotype, with this switch being a common pathology in cardiovascular diseases. The aim of this study was to explore the joint influence of age and hypertension on thoracic aortic smooth muscle phenotypic switching and the balance of Akt and mitogen-activated protein kinase (MAPK) signaling during this switch. Different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used to establish hypertension and aging models. The phenotypic state was determined by detecting the marker proteins α-SM-actin, calponin, and osteopontin (OPN) via immunohistochemical staining and Western blot. Signaling proteins associated with the Akt and MAPK pathways were detected in rat thoracic aorta using Western blot. Both aging and hypertension caused a decrease in contractile (differentiated) phenotype markers (α-SM-actin and calponin), while the synthetic (proliferative or de-differentiated) phenotype maker was elevated (OPN). When combining hypertension and aging, this effect was enhanced, with Akt signaling decreased, while MAPK signaling was increased. These results suggested that VSMCs phenotype switching is modulated by a balance between Akt and MAPK signaling in the process of aging and hypertension., Lin Zhang, Zhaoxia Xu, Ying Wu, Jingwen Liao, Fanxing Zeng, Lijun Shi., and Obsahuje bibliografii
Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main pathogenetic factor in intrauterine growth restriction, elevates fetoplacental vascular resistance (and vasoconstrictor reactivity) and thus, presumably, reduces placental blood flow. We thus hypothesized that alcohol may affect the fetus - in addition to other mechanisms - by altering fetoplacental vascular resistance and/or reactivity. Using isolated, double-perfused rat placenta model, we found that maternal alcohol intake in the last third of gestation doubled the vasoconstrictor responses to angiotensin II but did not affect resting vascular resistance. Reactivity to acute hypoxic challenges was unchanged. Chronic maternal alcohol intake in a rat model alters fetoplacental vasculature reactivity; nevertheless, these changes do not appear as serious as other detrimental effects of alcohol on the fetus., V. Jakoubek, V. Hampl., and Obsahuje bibliografii
Aldosterone plays a key role in maintaining the homeostasis of the whole organism. Under some circumstances, aldosterone can contribute to the progression of cardiovascular diseases, including coronary artery disease. This study demonstrates that aldosterone associates negatively with some lipidogram parameters and positively with the concentration of homocysteine. These associations are characteristic for coronary artery disease and are not present in control subjects. The findings also indicate that in vitro aldosterone stimulates homocysteine production by rat adrenal glands, which may explain the associations observed with coronary artery disease. Moreover, we have found that aldosterone significantly modulates in vitro platelet reactivity to arachidonate and collagen - aldosterone increases the pro-aggregatory action of collagen, but decreases the pro-aggregatory potential of arachidonate. Therefore, the findings of these in vitro and ex vivo experiments indicate the existence of new pathways by which aldosterone modulates lipid- homocysteine- and platelet-dependent atherogenesis., K. Karolczak, P. Kubalczyk, R. Glowacki, R. Pietruszynski, C. Watala., and Seznam literatury
Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w. ) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated wa ter. In the alendronate group significant reductions of choleste rol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system., Ľ. Cibičková, R. Hyšpler, N. Cibiček, E. Čermáková, V. Palička., and Obsahuje bibliografii
Growth factors are powerful molecules that regulate cellular growth, proliferation, healing, and cellular differentiation. A delivery matrix that incorporates growth factors with high loading efficiencies, controls their release, and maintains bioactivity would be a powerful tool for regenerative medicine. Alginate has several unique properties that make it an excellent platform for the delivery of proteins. Mild gelling conditions can minimize the risk of protein denaturation; moreover, alginate can serve as protection from degradation until protein release. Various modifications have been proposed to tune alginate binding and release proteins, simultaneously adjusting alginate degradability, mechanical stiffness, swelling, gelation properties and cell affinity. The primary objective of this article is to review the literature related to recent advances in the application of alginate matrices in protein delivery in regenerative medicine. A special emphasis is put on the relevance of delivery of growth factors and chemokine., E. Wawrzyńska, D. Kubies., and Obsahuje bibliografii
In the present work neonatal male and female Wistar rats were treated intraperitoneally with monosodium glutamate (MSG 2 mg/kg b.w.) or saline (controls) daily for 4 day after birth. At the age of 30 and 80 days, the alkaline phosphatase activity (AP) in the brush border of individual enterocytes, the body fat content and Lee´s index of obesity were analyzed. Microdensitometrical quantification of AP was significantly increased on day 30 in males (P<0.01) and on day 80 in MSG-treated male and female rats (P<0.001) as compared to the controls. MSG administration also increased the body fat weight and the obesity index significantly (P<0.001) in 80-day-old animals, but was without any significant effect on their food intake. Our results showed that a) neonatal MSG-treatment may significantly change the intestinal function and b) the investigation of the intestinal enzyme activities may be important in further studies on MSG-induced and other forms of obesity., Š. Mozeš, Ľ. Lenhardt, A. Martinková., and Obsahuje bibliografii
The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors., E. Biroš, I. Kalina, A. Kohút, E. Bogyiová, J. Šalagovič, I. Šulla., and Obsahuje bibliografii
The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of • VO2 kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % • VO2 max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. Allopurinol intake caused increase in resting xanthine and hypoxanthine plasma concentrations, however it did not affect the slow component of oxygen uptake during exercise. Exercise elevated plasma inosine, hypoxanthine, and xanthine. Moreover, exercise induced a decrease in total antioxidant status, and sulfhydryl groups. However, no interaction treatment x time has been observed. Short term severe intensity exercise induces oxidative stress, but xanthine oxidase inhibition does not modify either the kinetics of oxygen consumption or reactive oxygen species overproduction., R. A. Olek ... [et al.]., and Obsahuje seznam literatury
Ivermectin acts as a positive allosteric regulator of several ligand gated channels including the glutamate-gated chloride channel (GluCl), γ-aminobutyric acid type-A receptor, glycine receptor, neuronal α 7-nicotinic receptor and purinergic P2X4 receptor. In most of the ivermect in-sensitive channe ls, the effects of ivermectin include the potentiation of agonist-induced currents at low concentrations and channel opening at higher concentrations. Based on mutagenesis, electrophysiological recordings and functional an alysis of chimeras between ivermectin-sensitive and ivermectin-insensitive receptors, it has been concluded that ivermectin acts by insertion between transmembrane helices. The three-dimensional structure of C. elegans GluCl complexed with ivermectin has revealed the details of the ivermectin-binding site, however, no generic motif of amino acids could accurately predict ivermectin binding site for other ligand gated channels. Here, we will review what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structur al determinants underlying potentiation of the P2X4 receptor channel., H. Zemkova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Endothelin-1 (ET-1) acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ETA and ETB receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ETA or ETB receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ETA expression which was attenuated by saline and centhaquin; ETB expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ETA expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ETB expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ETA and ETB receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy., S. Briyal, R. Gandhakwala, M. Khan, M. S. Lavhale, A. Gulati., and Seznam literatury
STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice., C. P. Chu, B. R. Cui, H. Kannan, D. L. Qiu., and Obsahuje bibliografii
The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA- damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured an imals when compared to acute and chronic sham groups. Our da ta has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy., T. Dagci, G. Armagan, S. Konyalioglu, A. Yalcin., and Obsahuje bibliografii
Both brain and peripheral nitric oxide (NO) play a role in the control of blood pressure and circ ulatory homeostasis. Central NO production seems to counteract angiotensin II-induced enhancement of sympathetic tone. The aim of our study was to evaluate NO synthase (NOS) activity and protein expression of its three isoforms - neuronal (nNOS), endothelial NOS (eNOS) and inducible (iNOS) - in two brain regions involved in blood pressure control (diencephalon and brainstem) as well as in the kidney of young adult rats with either genetic (12-week-old SHR) or salt- induced hypertension (8-week-old Dahl rats). We have demonstrated reduced nNOS and iNOS expression in brainstem of both hypertensive models. In SHR this abnormality was accompanied by attenuated NOS activity and was corrected by chronic captopril treatment which prevented the development of genetic hypertension. In salt hypertensive Dahl rats nNOS and iNOS expression was also decrea sed in the diencephalon where neural structures important for salt hypertension development are located. As far as peripheral NOS activity and expression is concerned, renal eNOS expression was considerably reduced in both genetic and salt-induced hypertension. In conclusions, we disclosed similar changes of NO system in the brainstem (but not in the diencephalon) of rats with genetic and salt-induced hypertension. Decreased nNOS ex pression was associated with increased blood pressure due to enhanced sympathetic tone., S. Hojná, J. Kuneš, J. Zicha., and Obsahuje bibliografii
The aim was to study the blood-brain permeability according to the distribution in the rat brain of Evans blue (EB) and sodium fluorescein (NaFl) administered by an intracarotid injection. Eighteen animals were divided into six groups according to the state of the blood-brain barrier (BBB) at the moment when the dyes were being applied. In the first two groups, the BBB was intact, in groups 3 and 4 the barrier had been opened osmotically prior to the application of the dyes, and in groups 5 and 6 a cellular edema was induced by hyperhydration before administration of the dyes. The intracellular and extracellular distribution of the dyes was studied by fluorescence microscopy. The histological picture thus represented the morphological correlate of the way BBB permeability had been changed before the application of the dyes., P. Kozler, J. Pokorný., and Obsahuje bibliografii
Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR - STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCEassociated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism., Róbert Čendula, Nikola Chomaničová, Adriana Adamičková, Andrea Gažová, Ján Kyselovič, Marek Máťuš., and Obsahuje bibliografii
b1_Essential hypertension is a multifactorial disorder which belongs to the main risk factors responsible for renal and cardiovascular complications. This review is focused on the experimental research of neural and vascular mechanisms involved in the high blood pressure control. The attention is paid to the abnormalities in the regulation of sympathetic nervous system activity and adrenoceptor alterations as well as the changes of membrane and intracellular processes in the vascular smooth muscle cells of spontaneously hypertensive rats. These abnormalities lead to increased vascular tone arising from altered regulation of calcium influx through L-VDCC channels, which has a crucial role for excitation-contraction coupling, as well as for so-called “calcium sensitization” mediated by the RhoA/Rho-kinase pathway. Regulation of both pathways is dependent on the complex interplay of various vasodilator and vasoconstrictor stimuli. Two major antagonistic players in th e regulation of blood pressure, i.e. sympathetic nervous system (by stimulation of adrenoceptors coupled to stimulatory and inhibitory G proteins) and nitric oxide (by cGMP signaling pathway), elicit their actions via the control of calcium influx through L-VDCC. However, L-type calcium current can also be regulated by the changes in membrane potential elicited by the activation of potassium channels, the impaired function of which was detected in hypertensive animals. The dominant role of enhanced calcium influx in the pathogenesis of high blood pressure of genetically hypertensive animals is confirmed not only by therapeutic efficacy of calcium antagonists but especially by the absence of hypertension in animals in which L-type calcium current was diminished by pertussis toxin-induced inactivation of inhibitory G proteins., b2_ there is considerable information on th e complex neural and vascular alterations in rats with established hypertension, the detailed description of their appearance during the induction of hypertension is still missing., M. Pintérová, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
Prolonged exposure to alveolar hypoxia induces physiological changes in the pulmonary vasculature that result in the development of pulmonary hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is influenced by vasoconstrictor and vasodilator factors secreted from the endothelium, lung parenchyma and in the circulation. During chronic hypoxia, production of vasoconstrictors such as endothelin-1and angiotensin II is enhanced locally in the lung, while synthesis of vasodilators may be reduced. Altered reactivity to these vasoactive agonists is another physiological consequence of chronic exposure to hypoxia. Enhanced contraction in response to endothelin-1 and angiotensin II, as well as depressed vasodilation in response to endothelium-derived vasodilators, has been documented in models of hypoxic pulmonary hypertension. Chronic hypoxia may also have direct effects on pulmonary vascular smooth muscle cells, modulating receptor population, ion channel activity or signal transduction pathways. Following prolonged hypoxic exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current, membrane depolarization, elevation in resting cytosolic calcium and changes in signal transduction pathways. These changes in the electrophysiological parameters of pulmonary vascular smooth muscle cells are likely associated with an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary arterial myocyte function, changes in synthesis of vasoactive factors and altered vasoresponsiveness to these agents may shift the environment in the lung to one of contraction instead of relaxation, resulting in increased pulmonary vascular resistance and elevated pulmonary arterial pressure., L. A. Shimoda, J. S. K. Sham, J. T. Sylvester., and Obsahuje bibliografii