Fibroblast growth factor (FGF) signaling plays an important role during embryonic induction and patterning, as well as in modulating proliferative and hypertrophic growth in fetal and adult organs. Hemodynamically induced stretching is a powerful physiological stimulus for embryonic myocyte proliferation. The aim of this study was to assess the effect of FGF2 signaling on growth and vascularization of chick embryonic ventricular wall and its involvement in transmission of mechanical stretchinduced signaling to myocyte growth in vivo . Myocyte proliferation was significantly higher at the 48 h sampling interval in pressure-overloaded hearts. Neither Western blotting, nor immunohistochemistry performed on serial paraffin sections revealed any changes in the amount of myocardial FGF2 at that time point. ELISA showed a significant increase of FGF2 in the serum. Increased amount of FGF2 mRNA in the heart was confirmed by real time PCR. Blocking of FGF signaling by SU5402 led to decreased myocyte proliferation, hemorrhages in the areas of developing vasculature in epicardium and digit tips. FGF2 synthesis is increased in embryonic ventricular cardiomyocytes in response to increased stretch due to pressure overload. Inhibition of FGF signaling impacts also vasculogenesis, pointing to partial functional redundancy in paracrine control of cell proliferation in the developing heart., E. Krejci, Z. Pesevski, O. Nanka, D. Sedmera., and Obsahuje bibliografii
Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways., M. Antosova, D. Mokra, L. Pepucha, J. Plevkova, T. Buday, M. Sterusky, A. Bencova., and Obsahuje bibliografii
Early recognition of collapsing hemodynamics in pulmonary embolism is necessary to avoid cardiac arrest using aggressive medical therapy or mechanical cardiac support. The aim of the study was to identify the maximal acute hemodynamic compensatory steady state. Overall, 40 dynamic obstructions of pulmonary artery were performe d and hemodynamic data were collected. Occlusion of only left or right pulmonary artery did not lead to the hemodynamic collapse. When gradually obstructing the bifurcation, the right ventri cle end-diastolic area expanded proportionally to pulmonary artery mean pressure from 11.6 (10.1, 14.1) to 17.8 (16.1, 18.8) cm 2 (p<0.0001) and pulmonary artery mean pressure increased from 22 (20, 24) to 44 (41, 47) mmHg (p<0.0001) at the poin t of maximal hemodynamic compensatory steady state. Sim ilarly, mean arte rial pressure decreased from 96 (87, 101) to 60 (53, 78) mmHg (p<0.0001), central venous pressure increased from 4 (4, 5) to 7 (6, 8) mmHg (p<0.0001), heart rate increased from 92 (88, 97) to 147 (122, 165) /min (p<0.0001), contin uous cardiac output dropped from 5.2 (4.7, 5.8) to 4.3 (3.7, 5.0) l/min (p=0.0023), modified shock index increased from 0.99 (0.81, 1.10) to 2.31 (1.99, 2.72), p<0.0001. In conclusion, in stead of continuous cardiac output all of the analyzed parameters can sensitively determine the individual maximal compensatory response to obstructive shock. We assume their monitoring can be used to predict the critical phase of the hemodynamic status in routine practice., J. Kudlička ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Spatial navigation comprises a widely-studied complex of animal behaviors. Its study offers many methodological advantages over other approaches, enabling assessment of a variety of experimental questions and the possibility to compare the results across different species. Spatial navigation in laboratory animals is often considered a model of higher human cognitive functions including declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents was designed in our laboratory, originally named the place avoidance task, and later a modification of this approach was established and called active place avoidance task. It employs a continuously rotating arena, upon which animals are trained to avoid a stable sector defined according to room-frame coordina tes. This review describes the development of the place avoidance tasks, evaluates the cognitive processes associated with performance and explores the application of place avoidance in the testing of spatial learning after neuropharmacological, lesion and other experimental manipulations., A. Stuchlík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Clusterin is a heterodimeric glycoprotein with wide range of functions. To further explore its possible regulatory role in energy homeostasis and in adipose tissue, we measured plasma clusterin and its mRNA expression in subcutaneous adipose tissue (SCAT) of 15 healthy lean women, 15 obese women (OB) and 15 obese women with type 2 diabetes mellitus (T2DM) who underwent a 2-week very low-calorie diet (VLCD), 10 obese women without T2DM who underwent laparoscopic sleeve gastrectomy (LSG) and 8 patients with T2DM, 8 patients with impaired glucose tolerance (IGT) and 8 normoglycemic patients who underwent hyperinsulinemic euglycemic clamp (HEC). VLCD decreased plasma clusterin in OB but not in T2DM patients while LSG and HEC had no effect. Clusterin mRNA expression in SCAT at baseline was increased in OB and T2DM patients compared with controls. Clusterin mRNA expression decreased 6 months after LSG and remained decreased 12 months after LSG. mRNA expression of clusterin was elevated at the end of HE C compared with baseline only in normoglycemic but not in IGT or T2DM patients. In summary, our data suggest a possible local regulatory role for clusterin in the adipose tissue rather than its systemic involvement in the regulation of energy homeostasis., J. Kloučková, Z. Lacinová, P. Kaválková, P. Trachta, M. Kasalický, D. Haluzíková, M. Mráz, M. Haluzík., and Obsahuje bibliografii
Serum adipocyte fatty acid-binding protein (FABP-4) concentrations are linked to human obesity and other features of metabolic syndrome. Patients with Cushing's syndrome (CS) develop numerous features of metabolic syndrome due to chronic cortisol excess. Here we tested the hypothesis that chronically increased cortisol levels in CS patients may alter circulating levels of FABP-4. Fourteen patients with CS, 19 patients with simple obesity (OB) and 36 healthy control subjects (C) were included in the study. Serum FABP-4 concentrations were significantly higher in both CS and OB patients relati ve to C group, but they did not differ between CS and OB groups. In a combined population of all groups, serum FABP-4 levels correlated positively with BMI, body fat content, serum glucose, triglycerides, HbA1c and HOMA index and were inversely relate d to HDL-cholesterol, resting energy expenditure and freeT3 levels. We conclude that FABP-4 levels are significantly increased in both patients with simple obesity and obese patients with Cushing's syndrome. We suggest that increased FABP-4 concentrations in CS patients are rather due to their excessive fat accumulation and related metabolic abnormalities than due to a direct effect of cortisol on FABP-4 production., V. Ďurovcová, J. Marek, V. Hána, M. Matoulek, V. Zikán, D. Haluzíková, P. Kaválková, Z. Lacinová, M. Kršek, M. Haluzík., and Obsahuje bibliografii
The objective of this study was to measure plasma fibroblast growth factor 21 and 19 (FGF21 and FGF19) levels in patients with Cushing's syndrome (CS) and to compare it with those of lean control subjects (C) and patients with obesity (OB). Fourteen untreated patients with CS, 19 patients with OB and 36 controls were included in the study. Plasma FGF21 and FGF19 levels were measured by ELISA kits, other hormonal and biochemical parameters were measured by standard laboratory methods. Plasma FGF19 did not significantly differ among the studied groups. Plasma FGF21 levels were significantly higher in both CS and OB groups relative to C group but they did not differ between CS and OB groups. In a combined population of all three groups FGF21 levels positively correlated with BMI, waist circumference and percentage of total and truncal fat mass. Less prominent inverse relationship with these parameters was found for FGF19. Neither FGF21 nor FGF19 were significantly related to cortisol concentrations. Increased FGF21 concentrations in both patients with CS and OB relative to lean subjects suggest that excessive body fat and/or related metabolic abnormalities rather than direct effects of cortisol are responsible. In contrast neither obesity nor hypercortisolism significantly affected FGF19 concentrations., V. Ďurovcová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The impact of anesthetic agen ts on endocrine and metabolic factors is an important issue. The present study has compared the effects of a short-term exposure to diethyl ether, isoflurane, or CO2 on plasma corticosterone, insulin and glucose concentrations since the duration of anesthetic exposure may have an effect on those factors. Male rats were divided into fed and fasted groups. The experimental rats were briefly exposed to diethyl ether, isoflurane, or CO2 (the degree of anesthesia was identical), while a control group was not exposed to the anesthetics. In the fed rats, diethyl ether exposure increased the levels of plasma glucose. CO2 exposure decreased plasma corticosterone and increased plasma glucose levels. Isoflurane exposure caused no changes in plasma corticosterone, glucose, or insulin levels. In the fasted rats, diethyl ether exposure increased plasma corticosterone and reduced plasma insulin levels. The plasma corticosterone and insulin levels were significantly increased by CO2 exposure. Isoflurane exposure decreased plasma insulin levels. A brief exposure to either diethyl ether or CO2 changed the plasma corticosterone, glucose, and insulin levels in fed and/or fasted rats. However, isoflurane exposure had the least effect on the concentration of these factors in both the fed and fasted states., H. Zardooz, F. Rostamkhani, J. Zaringhalam, F. Faraji Shahrivar., and Obsahuje bibliografii
Tissue betaine is an intracellular osmolyte that also provides a store of labile methyl groups. Despite these important biological roles, there are few data regarding tissue betaine content. We measured the betaine concentration of plasma and various tissues (brain, heart, lungs, liv er, kidney, spleen, intestine, reproductive tissues, skeletal muscle and skin) in male and female rats and assessed whether there were any gender-specific differences in betaine content or distribution and whether there was any relationship between tissue accumulation and plasma levels. Betaine was highest in the liver and kidney with values ranging from 1.6 to 9.5 mmol/l and 2.0 to 5.4 mmol/l, respectively. Plasma betaine concentrations were significantly lower than tissue levels except in the brain ( ≈ 25 % of plasma) and skeletal muscle (similar to pl asma). Regression analysis of the combined male and female data revealed a significant plasma-related accumulation of betaine in the heart, skin and skeletal muscle, while the lung, liver, kidney, spleen, and intestine showed significant plasma-related and plasma- independent accumulations of be taine. The betaine content of the skin, liver and kidney was no t significantly different between males and females, but in plasma and all tissues analyzed it was significantly higher in males (P<0.01)., S. Slow, M. Lever, S. T. Chambers, P. M. George., and Obsahuje bibliografii
Hepcidin, a recently discovered antimicrobial peptide synthesized in the liver, was identified to be the key mediator of iron metabolism and distribution. Despite our knowledge of hepcidin increased in recent years, there are only limited data on hepcidin regulation during systemic inflammatory response in human subjects. In a prospective study, the time course of plasma hepcidin was analyzed in relations to six inflammatory parameters - plasma cytokines and acute-phase proteins in patients undergoing uncomplica ted pulmonary endarterectomy. Twenty-four patients (males, aged 52.6±10.2 years, treated with pulmonary endarterectomy in a deep hypothermic circulatory arrest) were enrolled into study. Hepcidin, interleukin (IL)-6, IL- 8, tumor necrosis factor-α, C-reactive protein, α1-antitrypsin and ceruloplasmin arterial concentrations were measured before surgery and repeatedly within 120 h post-operatively. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. In a postoperative period, hepcidin increased from preoperative level 8.9 ng/ml (6.2-10.7) (median and interquartile range) to maximum 16.4 ng/ml (14.1-18.7) measured 72 h after the end of su rgery. Maximum post-operative concentrations of hepcidin correlated positively with maximum IL-6 levels. Both hepcidin and IL-6 maximum concentrations correlated positively with extracorporeal circulation time. In conclusions, the study demonstrated that plasma hepcidin is a positive acute-phase re actant in relation to an uncomplicated large cardiac surgery. Hepcidin increase was related to IL-6 concentrations and to the duration of surgical procedure. Our clinical findings are in conformity with recent experimental studies defining hepcidin as a type II acute-phase protein., P. Maruna, M. Vokurka, J. Lindner., and Obsahuje bibliografii a bibliografické odkazy