Western moral and political theorists have recently devoted considerable attention to the perceived victimisation of women by non-western cultures. In this paper, the author argues that conceiving injustice to poor women in poor countries primarily as a matter of their oppression by illiberal cultures presents an understanding of their situation that is crucially incomplete. This incomplete understanding distorts Western theorists’ comprehension of our moral relationship to women elsewhere in the world and so of our theoretical task. It also impoverishes our assumptions about the intercultural dialogue necessary to promote global justice for women., Alison M. Jaggar, and Anglické resumé
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
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
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
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
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
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
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
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
Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa., J. Křížová, M. Dolinková, Z. Lacinová, Š. Sulek, R. Doležalová, J. Housová, J. Krajíčková, D. Haluzíková, L. Bošanská, H. Papežová, M. Haluzík., 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
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
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
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
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 oxidative stress hypothesis of aging suggests that accumulation of oxidative damage is a key factor of the alterations in physiological function during aging. We studied age-related sensitivity to oxidative modifications of proteins and lipids of cardiac sarcoplasmic reticulum (SR) isolated from 6-, 15- and 26-month-old rats. Oxidative stress was generated in vitro by exposing SR vesicles to 0.1 mmol/l FeSO4/EDTA + 1 mmol/l H2O2 at 37 °C for 60 min. In all groups, oxidative stress was associated with decreased membrane surface hydrophobicity, as detected by 1-anilino-8-naphthalenesulfonate as a probe. Structural changes in SR membranes were accompanied by degradation of tryptophan and significant accumulation of protein dityrosines, protein conjugates with lipid peroxidation products, conjugated dienes and thiobarbituric acid reactive substances. The sensitivity to oxidative damage was most pronounced in SR of 26-month-old rat. Our results indicate that aging and oxidative stress are associated with accumulation of oxidatively damaged proteins and lipids and these changes could contribute to cardiovascular injury., E. Babušíková, M. Jeseňák, D. Dobrota, N. Tribulová, P. Kaplán., and Obsahuje bibliografii a bibliografické odkazy
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