We studied the changes in seru m fibroblast growth factor-21 (FGF-21) concentrations, its mR NA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surger y, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113. 95) pg/ml and it increased during surgery with peak 6 ho urs after its end [385.5 (274.55-761.65) pg/ml, p<0.001], and return ed to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours afte r the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress., T. Kotulák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Previously, increased diameter and enhanced myogenic tone were seen after 2-week 45º head-up (HUT2) in the rat. We studied the reversibility and the effect of extended tilt on this phenomenon using two experimental groups: HUT2 plus 2-week horizontal (HUT2HOR2), and 4-week tilting (HUT4). 4-weeks in normal cages (NC4) served as control. Diameter of saphenous vein (SV) in 2-20 mm Hg pressure range, wall and media thickness, endothelial and smooth muscle cell densities, and cell proliferation were measured. The diameter of SV from HUT4 was significantly larger compared with HUT2HOR2 or NC4 within the whole pressure range both in Krebs-Ringer (870.4±21.3 vs. 778.2±24.9 and 771.6±28.1 μm at 10 mm Hg, respectively) and in Ca2+-free solution. Myogenic and norepinephrine-induced vascular tone, wall and media thickness did not differ among the three groups. Endothelial cell density decreased in HUT4 (10.7±1.2) vs. HUT2HOR2 (15.1±1.0) and NC4 (15.3±0.6), while that of smooth muscle was unchanged. No cell proliferation marker was seen. In conclusion, both increased diameter and enhanced myogenic tone of SV seen in HUT2 proved to be reversible. HUT4 resulted in increased SV diameter, similarly to HUT2, however, vascular tone was not amplified. This suggests that a prolonged orthostatic load may readjust the function of smooth muscle., G. Raffai, C. Lódi, G. Illyés, G. Nádasy, E. Monos., and Obsahuje bibliografii a bibliografické odkazy
The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome., F. Schinzari, M. Tesauro, C. Cardillo., and Seznam literatury
Erythropoietin (EPO), known for its role in erythroid differentiation, has been suggested to have a direct protective role against a variety of neurotoxic insults. In the present study, we investigated the expression of EPO receptor (EPOR) and the number of EPORpositive cells in three encephalic regions (ventral mesencephalon, striatum, cortex) following lesion induced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 mice underwent intraperitoneal injection of MPTP at 24 h intervals for 5 days, and their brains were examined 1, 2, 4, 7, 14 or 21 days after the last injection. Western blot and immunohistochemistry analysis revealed that EPOR was dramatically up-regulated in the ventral mesencephalon, 4 days after MPTP insult until the day 21. In contrast, there was a baseline level of EPOR in the striatum and cortex. At subsequent time points after MPTP injury, the levels of EPOR in the two regions were not statistically different compared with those in normal animals. These results suggest that the regional specific up-regulation of EPOR at an early stage after MPTP stimulus may represent a pro-survival mechanism against neurotoxin injury in Parkinsonian model., Y. Wu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to osteoarthritis could be useful for better understanding of its pa thogenesis and therapy. In this study we have investigated a long-term pattern of expression and production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection produced thermal hyperalgesia (assessed by the plantar test) and tactile allodynia (measured with von Frey hairs). The pain measures reached maximum on the 5th day, then re mained relatively stable. The expression of spinal COX-2 mR NA reached maximum on day 5 (5.2 times; P<0.001) and remain ed increased until day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression of both genes was almost equal. The production of both proteins was almost similar at the beginning of the experiment. The highest production of COX-2 protein was observed on day 5 after the induction of osteoarthritis (increased 3.9 times). The levels of COX-1 protein increased gradually with maximum on day 31 (3.4 times). The present findings indicate that not only expression of COX-2 mRNA but also that of COX-1 mRNA is significantly increased in the spine during osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of spinal COX-1 may be important in osteoarthritis pain., M. Procházková, P. Zanvit, T. Doležal, L. Prokešová, M. Kršiak., and Obsahuje bibliografii
Anorexia nervosa (AN) is characterized by self-induced starvation leading to severe weight and fat loss. In the present study, we measured fasting plasma levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was determined according to homeostasis model assessment of insulin resistance (HOMA-R). Plasma resistin, leptin and insulin levels were significantly decreased, whereas plasma adiponectin levels were significantly increased in patients with AN compared to the C. HOMA-R was significantly decreased in patients with AN compared to the C group. Plasma adiponectin and leptin concentrations negatively and positively correlated with the body mass index and percentage body fat in both groups. Plasma adiponectin levels were negatively related to plasma insulin levels in the AN group only. In conclusion, we demonstrated that AN is associated with significantly decreased plasma leptin and resistin levels, markedly increased plasma adiponectin levels and increased insulin sensitivity. Plasma leptin and adiponectin levels were related to the body size and adiposity. Hyperadiponectinemia could play a role in increased insulin sensitivity of patients with AN. Neither body size and adiposity nor insulin sensitivity are the major determinants of plasma resistin levels in AN. and Obsahuje bibliografii a bibliografické odkazy
Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm2 ). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis., Karolína Rozsívalová, Aneta Pierzynová, Helena Kratochvílová, Jaroslav Lindner, Michal Lipš, Tomáš Kotulák, Peter Ivák, Ivan Netuka, Martin Haluzík, Tomáš Kučera., and Obsahuje bibliografii
Autism is a disorder of neural development characterized by impairments in communication, social interaction, restricted interests and repetitive behavior. The etiology of autism is poorly understood, the evidence indicates that inflammation may play a key role. In autism a high prevalence of gastrointestinal disturbances is reported, that are linked to a low-grade chronic inflammation of the intestinal mucosa. High mobility group box 1 protein (HMGB1) is an intranuclear protein that can be passively released from necrotic cells or actively secreted under inflammatory conditions as alarmin or late proinflammatory cytokine. The objective of this study was to measure plasma levels of HMGB1 in individuals with autism and to analyze their association with gastrointestinal symptoms. The study involved 31 subjects with low-functioning autistic disorder aged 2-22 years and 16 healthy controls. Plasma HMGB1 levels were significantly higher in individuals with autism than in controls (13.8±11.7 ng/ml vs. 7.90±4.0 ng/ml, p<0.02). In subjects with plasma HMGB1levels higher than 11 ng/ml severe forms of GI disorders were more prevalent (83.3 %) than in subjects with lower levels (38.9 %, p<0.04). Results of the study support the involvement of the systemic low-grade inflammation in the pathomechanisms of autism and its possible association with GI symptoms., K. Babinská, M. Bucová, V. Ďurmanová, S. Lakatošová, D. Jánošíková, J. Bakoš, A. Hlavatá, D. Ostatníková., and Obsahuje bibliografii
Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 agecorresponding female controls with the use of gas chromatography - mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A γ-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3β,7α,17β-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity., R. Kanceva, L. Stárka, L. Kancheva, M. Hill, M. Veliková, E. Havrdová., and Obsahuje bibliografii
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a technique used in patients with severe heart failure. The aim of this study was to evaluate its effects on left ventricular afterload and fluid accumulation in lungs with electrical impedance tomography (EIT). In eight swine, incremental increases of extracorporeal blood flow (EBF) were applied before and after the induction of ischemic heart failure. Hemodynamic parameters were continuously recorded and computational analysis of EIT was used to determine lung fluid accumulation. With an increase in EBF from 1 to 4 l/min in acute heart failure the associated increase of arterial pressure (raised by 44 %) was accompanied with significant decrease of electrical impedance of lung regions. Increasing EBF in healthy circulation did not cause lung impedance changes. Our findings indicate that in severe heart failure EIT may reflect fluid accumulation in lungs due to increasing EBF., Michaela Popková, Eduard Kuriščák, Pavel Hála, David Janák, Leoš Tejkl, Jan Bělohlávek, Petr Ošťádal, Petr Neužil, Otomar Kittnar, Mikuláš Mlček., and Obsahuje bibliografii