Clinical studies showed that GABAB receptor agonists improve symptoms in patients with gastroesophageal reflux disease. One proposed mechanism of this effect is direct inhibition of the gastroesophageal vagal tension mechanosensors by GABAB agonists leading to reduction of reflux. In addition to tension mechanosensors, the vagal nodose ganglion supplies the esophagus with nociceptive C-fibers that likely contribute to impairment of esophageal reflex regulation in diseases. We hypothesized that GABAB agonists inhibit mechanically-induced activation of vagal esophageal nodose C-fibers in baseline and/or in sensitized state induced by inflammatory mediators. Ex vivo extracellular recordings were made from the esophageal nodose C-fibers in the isolated vagally-innervated guinea pig esophagus. We found that the selective GABAB agonist baclofen (100- 300 μM) did not inhibit activation of esophageal nodose C-fibers evoked by esophageal distention (10-60 mmHg). The mechanical response of esophageal nodose C-fibers can be sensitized by different pathways including the stimulation of the histamine H1 receptor and the stimulation the adenosine A2A receptor. Baclofen failed to inhibit mechanical sensitization of esophageal nodose Cfibers induced by histamine (100 μM) or the selective adenosine A2A receptor agonist CGS21680 (3 nM). Our data suggest that the direct mechanical inhibition of nodose C-fibers in the esophagus is unlikely to contribute to beneficial effects of GABAB agonists in patients with esophageal diseases., M. Brozmanová, ... [et al.]., and Obsahuje seznam literatury
The benefit of percutaneous transluminal angioplasty (PTA) of transplant renal artery stenosis for ischemic nephropathy may be adversely affected by rejection or other complications. As a result, assessment of the effect of PTA on renal function or blood pressure is often difficult. In this paper, we evaluated the effect of PTA using the method of integrated glomerular filtration rate (GFR) based upon the area under the curve over a follow-up period (AUC0-t), to express the level of GFR in a simple manner despite its significant fluctuations. A similar procedure was used to evaluate mean arterial pressure (MAP). The method was employed to assess the outcome in 20 individuals before PTA, and 1, 3, 6, 9 and 12 months after PTA. In eight cases, rejection was detected while there was one case of glomerulonephritis in the graft during the follow-up period. Evaluation (AUCCcr)0-12 related to the integrated pre-PTA value of Ccr [(Ccr)0 x 12] revealed a rise in GFR by more than 20 % in 65 % of cases. No improvement was observed in seven individuals with post-PTA complications. When assessing the integrated value of MAP, success of PTA (a reduction by at least 10 %) was found in 85 % of cases. No significant correlation was found between the relative changes of integrated GFR and MAP. Our data suggest that evaluation of the integrated value of GFR or MAP on the basis of AUC0-t allows to characterize, in a simple manner, the level of graft function and MAP throughout the follow-up period in individual cases. Furthermore, it may provide additional information on the average values obtained at different time intervals after the therapeutic procedure., J. Stříbrná, O. Schück, J.H. Peregrin, D. Krajíčková, J. Skibová., and Obsahuje bibliografii
We investigated the utility of strain, strain rate, and tissue Doppler imaging (TDI) for the evaluation of the right ventricle (RV) impairment in patients with a hypertrophic obstructive cardiomyopathy (HOCM) who underwent a successful alcohol septal ablation (ASA) and were without RV hypertrophy. A group of 19 patients suffering from HOCM with 22 controls was compared. The parameters of TDI were evaluated in mitral and tricuspid annulus. Strain and strain rate derived from TDI were assessed in an apical free wall of RV, as well as in basal segments of the left ventricle. Between both groups, there were significant differences only in isovolumic pre-ejection time (79.2±17.3 ms vs. 58.5±8.1 ms, p<0.01), isovolumic relaxation time (104.7±26.2 ms vs. 77.3±24.5 ms, p<0.01), myocardial performance (Tei) index measured from TDI (0.61±0.14 vs. 0.49±0.09, p<0.01), and early peak diastolic velocity of TDI (10.6±1.67 cm/s vs. 12.6±2.21 cm/s; p<0.05). Our results suggest the impairment of both systolic and diastolic RV function in patients suffering from HOCM. TDI-related parameters appear to be more sensitive than strain and strain rate for evaluation., D. Zemánek ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Although many studies have investigated the relationships of several adipokines to metabolic syndrome (MetS), the interrelationships of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF 21) have not been described in detail. We examined 209 asymptomatic dyslipidemic patients divided into MetS+ (n=73) and MetS- (n=136) groups. The aim of study was to evaluate the relationships between observed adipokines, to compare the levels of total ADP, A-FABP and FGF 21 in individuals with and without MetS, and to elucidate the relationships of individual adipokines to lipid parameters, markers of insulin resistance and endothelial hemostatic markers in these groups. In MetS+ group, we found the independent positive association ADP with A-FABP (beta=0.4888, p=0.0382), A-FABP with FGF 21 (beta=0.3811, p=0.0002) and von Willebrand factor (beta=0.4502, p=0.0013), and FGF 21 with A-FABP (bet a=0.4422, p=0.0002). Our study has confirmed the well-established risk profile of subjects with MetS, although clinically asymptomatic. MetS+ patients had also lower levels of ADP and higher levels of A-FABP and FGF 21. Our study evaluated the interrelationships of ADP, A-FABP and FGF 21 in asymptomatic dyslipidemic subjects with diagnosis of MetS. Especially strong association between A-FABP and FGF 21 needs to be clarified in further studies., D. Novotny ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The effects of environmental salinity on physiological responses, growth, and survival of the Gulf corvina, C. othonopterus, were evaluated in a 6-week completely randomized design experiment. Corvina (17.2±2.3 g mean initial body weight) were subjected to salinities of 5, 15, 25, and 35 ‰ and fed a commercial feed with protein and lipid contents of 46 and 14 %, respectively. Plasma osmolality increased significantly with salinity, ranging from 335.1±5.3 mOsm/kg in fish maintained at 5 ‰, to 354.8±6.8 mOsm/kg in fish kept in seawater, while a significant inverse relationship was observed between salinity and moisture content of whole fish, ranging from 73.8±0.7 (measured at 5 ‰) to 76.9±1.0 % (measured at 35 ‰). In spite of this, growth indices (final weight, weight gain, specific growth rate, condition factor, survival) were not altered, suggesting that, like other members of the family Sciaenidae, the Gulf corvina is a strong osmoregulator. The isosmotic point for this species was estimated to correspond to a salinity of 9.8 ‰. The present study represents the first set of experimental data on salinity tolerance of C. othonopterus and confirms the euryhalinity of this species., M. Perez-Velazquez, P. Urquidez-Bejarano, M. L. González-Félix, C. Minjarez-Osorio., and Obsahuje bibliografii
The purpose of this study was to investigate the occurrence and time-course of apoptosis in soleus skeletal muscle during the first 48 hours of unloading. Fifty Charles River mice were randomly divided into five groups (n=10 each) according to the time of hindlimb suspension (HS). Mice we re suspended for 0 (Control), 6 (6HS), 12 (12HS), 24 (24HS), and 48 hours (48HS). Soleus muscle atrophy was confirmed by a significant decrease of 20 % in muscle-wet weight and of 5 % in the ratio protein concentration/muscle wet-weight observed after 48 hours of unloading. The apoptotic index, the AIF (apoptosis-inducing factor) and p53 expression presented th eir uppermost value (304 %, 241 % and 246 %, respectively) at 24HS, and were preceded by the highest activity of caspase-3 and -8 at 12HS (170 % and 218 %, respectively) and of Bax/Bcl-2 content at 6HS (160 %). There were no marked ultrastructural alterations until 24 hours of simulated weightlessness. Lysosomal autophagic activity and infiltration of phagocytic cells were observed at 24HS and 48HS and might have contributed to the degenerative changes noticed in both groups. Though not consistently supported by morphological evidences, the biochemical parameters sustain the concept that the occurrence of apoptosis parallels the soleus atrophic response in its early phase., R. Ferreira, M. J. Neuparth, R. Vittorino, H. J. Appell, F. Amado, J. A. Duarte., and Obsahuje bibliografii a bibliografické odkazy
Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA., J. Tumova, M. Andel, J. Trnka., and Obsahuje bibliografii
The aim of this study was to determine whether excessive oxygen uptake (V.o2) occurs not only during exercise but also during recovery after heavy exercise. After previous exercise at zero watts for 4 min, the main exercise was performed for 10 min. Then recovery exercise at zero watts was performed for 10 min. The main exercises were moderate and heavy exercises at exercise intensities of 40 % and 70 % of peak V.o2, respectively. V.o2 kinetics above zero watts was obtained by subtracting V.o2 at zero watts of previous exercise (ΔV.o2). ΔV.o2 in moderate exercise was multiplied by the ratio of power output performed in moderate and heavy exercises so as to estimate the ΔV.o2 applicable to heavy exercise. The difference between ΔV.o2 in heavy exercise and ΔV.o2 estimated from the value of moderate exercise was obtained. The obtained V.o2 was defined as excessive V.o2. The time constant of excessive V.o2 during exercise (1.88±0.70 min) was significantly shorter than that during recovery (9.61±6.92 min). Thus, there was excessive V.o2 during recovery from heavy exercise, suggesting that O2/ATP ratio becomes high after a time delay in heavy exercise and the high ratio continues until recovery., T. Zano, T. Yunoki, R. Matsuura, T. Arimitsu, T. Kimura., and Obsahuje bibliografii a bibliografické odkazy
Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed., D. Marešová, I. Valkounová, K. Jandová, J. Bortelová, S. Trojan., and Obsahuje bibliografii
Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there are characteristic rapid transient changes of intracellular Ca2+ concentration ([Ca2+]i), while the resting cytosolic [Ca2+]i concentration is low. It is mainly caused by two components of the Ca2+ signaling pathways: Ca2+ entry via L-type voltagedependent Ca2+ channels and dynamic involvement of intracellular stores. Proliferative VSMC phenotype is characterized by long-lasting [Ca2+]i oscillations accompanied by sustained elevation of basal [Ca2+]i. During the switch from contractile to proliferative phenotype there is a general transition from voltagedependent Ca2+ entry to voltage-independent Ca2+ entry into the cell. These changes are due to the altered gene expression which is dependent on specific transcription factors activated by various stimuli. It is an open question whether abnormal VSMC phenotype reported in rats with genetic hypertension (such as spontaneously hypertensive rats) might be partially caused by a shift from contractile to proliferative VSMC phenotype., E. Misárková, M. Behuliak, M. Bencze, J. Zicha., and Obsahuje bibliografii