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
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