Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1±10.3 to 32.3±10.9 to 38.1±10.3 μg.ml-1, p=0.015; from 0.52±0.09 to 0.58±0.06 to 0.62±0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r 2=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p<0.001, r 2=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients., I. Trojová, M. Kozarová, D. Petrasová, Z. Malachovská, I. Paranicová, P. Joppa, R. Tkacová., and Seznam literatury
Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous in the treatment of depressive disorder in comparison with tricyclic antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat cardiomyocytes in tissue culture. The results were compared with those from amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used. Both citalopram and amitriptyline exhibited the concentration-dependent inhibition of the L-type calcium channel current (ICa). Citalopram in concentrations of 3 mM and 10 mM inhibited peak calcium current by 2.7 % and 8 %, respectively. We demonstrated the same potency of citalopram and amitriptyline to inhibit ICa. These observations led us to conclude that citalopram and amitriptyline are drugs, which exhibit a similar potency for causing concentration-dependent inhibition of ICa., J. Hamplová-Peichlová, J. Krůšek, I. Paclt, J. Slavíček, V. Lisá, F. Vyskočil., and Obsahuje bibliografii
The effect of β3-adrenoceptor (β3-AR) agonists on adipocytes treated or not tr eated with signaling modulators has not been sufficiently elucidated. Using rat epididymal adipocytes (adipocytes) labeled with [ 32 P]orthophosphate, we found that treatment with the selective β3-AR agonist CL316243 (CL; 1 μ M) induces phosphatidylinositol (PI) 3,4,5-triphosphate (PI[3,4,5]P3) production and that this response is inhibited by adenosine deaminase (ADA, an adenosine -degrading enzyme; 2 U/ml), pertussis toxin (PTX, an inactivator of inhibitory guanine-nucleotide-binding protein; 1 μ g/ml), or wortmannin (WT, a PI -kinase inhibitor; 3 μ M). The results showed that CL induced PI(3,4,5)P 3 production in intact adipocytes and that this production was affected by signaling modulators. Taken together, our findings indicate that CL produces PI(3,4,5)P3 in an ADA-sensitive, PTX-sensitive, or WT-sensitive manner and will advance understanding of the effect of β3-AR agonists on adipocytes., Y. Ohsaka, Y. Nomura., and Obsahuje bibliografii
Erythromycin has a well-known dual effect on the contractility of the gastrointestinal system and recently has also been shown to inhibit contractions of the rat myometrium. The aim of the present study was to investigate the effects of clarithromycin on oxytocin, prostaglandin F2a (PGF2a) and KCl-induced contractions of human myometrium in vitro. Myometrial strips were obtained from pregnant women undergoing elective Cesarean section and the strips were suspended in a jacketed organ bath filled with Krebs solution at 37 oC (pH 7.4) and continuously aired with 95 % oxygen and 5 % carbon dioxide. Isometric contractions were measured using a force displacement transducer. Oxytocin, PGF2a, KCl and clarithromycin were applied to the tissue bath and the amplitude and frequency of contractions were evaluated at 20-min intervals. Freidmann analysis of variance, Kruskal Wallis and Wilcoxon Rank tests were used for statistical analysis of the data. Clarithromycin dose dependently inhibited the amplitude of contractions independent of the stimulus. Pre-treatment with apamin prevented clarithromycin-induced effects on amplitude and frequency of contractions. We conclude that the macrolide antibiotic clarithromycin may have a direct inhibitory effect on contractions of human myometrium., H. Celik, A. Ayar., and Obsahuje bibliografii
There exists no examination of what is the minimum anti - hypertensive threshold intensity for isometric exercise training. Twenty two normotensive participants were randomly assigned to training intensities at either 5 % or 10 % of their maximal contraction. Twenty participants completed the study. Clinical meaningful, but not statistically significant, reductions in systolic blood pressure were observed in both 5 % and 10 % groups -4.04 mm Hg (95 % CI -8.67 to +0.59, p=0.08) and -5.62 mm Hg (95 % CI -11.5 to +0.29, p=0.06) respectively after 6 weeks training. No diastolic blood pressure reductions were observed in either 5 % -0.97 mm Hg (95 % CI -2.56 to +0.62, p=0.20) or 10 % MVC +1.8 mm Hg (95 % CI -1.29 to +4.89, p=0.22) groups respectively after training. In those unable to complete isometr ic exercise at the traditional 30 % intensity, our results suggest there is no difference between 5 and 10 % groups and based on the principle of regression to the mean, this could mean both interventions induce a similar placebo-effect., N. C. L. Hess, D. J. Carlson, J. D. Inder, E. Jesulola, J. R. McFarlane, N. A. Smart., and Obsahuje bibliografii
The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (Rmax=53±4.7 %; pEC50=6±0.2) compared to endothelium-intact aortas (Rmax=100±9.9 %; pEC50=7±0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endotheliumindependent vasodilatation before the onset of HFD-induced insulin resistance., B. K. Chai, Y. S. Lau, B. J. Loong, M. M. Rais, K. N. Ting, D. M. Dharmani, S. K. Mohankumar., and Obsahuje bibliografii
The abnormal proliferation of vascular smooth muscle cells (VSMC) is thought to play a role in the pathogenesis of atherosclerosis. Adipocytes produce several bioactive paracrine substances that can affect the growth and migration of VSMCs. Our study focuses on the direct effect of the bioactive substances in conditioned media (CM) that was obtained by incubation with primary adipocyte-derived cell lines, including cell lines derived from both preadipocytes and from more mature cells, on the proliferation rate of human aortic smooth muscle cells (HAoSMCs). We used a Luminex assay to measure the adipokine content of the CM and showed that there was a higher concentration of monocyte chemoattractant protein-1 in renal preadipocyte-CM compared with the HAoSMC control (p<0.5). The addition of both renal preadipocyte- and epicardial adipocyte-CM resulted in the elevated production of vascular endothelial growth factor compared with the control HASoSMC CM (p<0.001). The adiponectin content in renal adipocyte-CM was increased compared to all the remaining adipocyte-CM (p<0.01). Moreover, the results showed a higher proliferation rate of HAoSMCs after co-culture with epicardial adipocyte-CM compared to the HAoSMC control (p<0.05). These results suggest that bioactive substances produced by adipocytes have a stimulatory effect on the proliferation of VSMCs., J. Ždychová, S. Čejsková, I. Králová Lesná, A. Králová, J. Malušková, L. Janoušek, L. Kazdová., and Obsahuje bibliografii
The processing of species-specific communication signals in the auditory system represents an important aspect of animal behavior and is crucial for its social interactions, reproduction, and survival. In this article the neuronal mechanisms underlying the processing of communication signals in the higher centers of the auditory system - inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC) - are reviewed, with particular attention to the guinea pig. The selectivity of neuronal responses for individual calls in these auditory centers in the guinea pig is usually low - most neurons respond to calls as well as to artificial sounds; the coding of complex sounds in the central auditory nuclei is apparently based on the representation of temporal and spectral features of acoustical stimuli in neural networks. Neuronal response patterns in the IC reliably match the sound envelope for calls characterized by one or more short impulses, but do not exactly fit the envelope for long calls. Also, the main spectral peaks are represented by neuronal firing rates in the IC. In comparison to the IC, response patterns in the MGB and AC demonstrate a less precise representation of the sound envelope, especially in the case of longer calls. The spectral representation is worse in the case of low-frequency calls, but not in the case of broad-band ca lls. The emotional content of the call may influence neuronal responses in the auditory pathway, which can be demonstrated by stimulation with time-reversed calls or by measurements performed under different levels of anesthesia. The investigation of the principles of the neural coding of species-specific vocalizations offers some keys for understanding the neural mechanisms underlying human speech perception., D. Šuta, J. Popelář, J. Syka., and Obsahuje bibliografii a bibliografické odkazy
We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO-dependent vasorelaxant effects and stimulate cardiac function. In the present study, we aim to investigate the effect of CPC on both nitric oxide (NO) and superoxide anions (O2-) production in cultured human endothelial cells. In addition, its effect on the bradykinin (BK)-induced NO production was also tested. The role and sources of O2- in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O2- signals were measured using electron paramagnetic resonance technique using specific spin trappings. Both, CPC and BK induced an in crease in NO production in human endothelial cells. The combination of both further enhanced NO release. The capacity of CPC plus BK to increase NO signal was blunted by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, and was enhanced in the presence either of superoxide dismutase or catalase. Moreover, CPC plus BK response was greater after inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol but it was not affected by rotenone. CPC did not affect O2- level either alone or after its increase upon lipopolysaccharide treatment. Finally, the capacity of BK alone to increase NO was enhanced either by apocynin or allopurinol. Altogether, these data demonstrate that CPC is able to directly increase NO production without affecting O2- and enhances the BK-induced NO production in human endothelial cells. The data highlight the ability of BK to stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive mechanisms that reduce its efficiency in increasing NO either alone or in the presence of CPC. These results bring pharmacological evidence for vascular protection by CPC via its potentiating effect of BK response in terms of endothelial NO release., A. Sall Diallo, M. Sarr, H. A. Mostefai, N. Carusio, M. Pricci, R. Andriantsitohaina., and Obsahuje bibliografii a bibliografické odkazy
Combined administration of drugs elevating extracellular adenosine, namely dipyridamole and adenosine monophosphate, together with granulocyte colony-stimulating factor was shown to enhance granulopoietic recovery in the bone marrow of mice treated with 5-fluorouracil. Enhanced regeneration was found both at the level of hematopoietic progenitor cells for granulocytes and macrophages and in the compartment of morphologically recognizable granulocyte precursors. The results might have positive clinical impact. The adjunct use of drugs elevating extracellular adenosine might reduce the cost expenditure of therapy with granulocyte colony-stimulating factor., M. Hofer, M. Pospíšil, L. Weiterová, V. Znojil, J. Vácha, J. Holá, A. Vacek, I. Pipalová., and Obsahuje bibliografii