Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF- 21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA., H. Hulejová ... [et al.]., and Obsahuje seznam literatury
Spatial tasks in rodents are commonly used to study general mechanisms of cognition. We review two groups of novel spatial tasks for rodents and discuss how they can extend our understanding of mechanisms of spatial cognition. The first group represents spatial tasks in which the subject does not locomote. Locomotion influences neural activity in brain structures important for spatial cognition. The tasks belonging to the first group make it possible to study cognitive processes without the interfering impact of locomotion. The second group represents tasks in which the subject approaches or avoids a moving object. Despite this topic is intensively studied in various animal species, little attention has been paid to it in rodents. Both groups of the tasks are powerful tools for addressing novel questions about rodent cognition., D. Klement, K. Blahna, T. Nekovářová., and Obsahuje bibliografii a bibliografické odkazy
Excessive production of reactive oxygen species (ROS) are implicated in the pathogenesis of numerous disease states. However, direct measurement of in vivo ROS in humans has remained elusive due to limited access to appropriate tissue beds and the inherently short half-lives and high reactivity of ROS. Herein, we describe a novel technique by which to measure in vivo ROS in human skeletal muscle. Microdialysis probes were inserted into the vastus lateralis of eight healthy volunteers. Amplex Ultrared, a highly specific fluorogenic substrate for hydrogen peroxide (H2O2), and horseradish peroxidase (HRP), were perfused through microdialysis probes, and outflowing dialysate was collected and fluorescence was measured. Extracellular H2O2 that crossed the microdialysis membrane was measured via fluorescence of the dialysate. Superoxide dismutase (SOD) was then added to the inflowing perfusion media to convert any superoxide crossing the microdialysis membrane to H2O2 within the microdialysis probe. Fluorescence significantly increased (P=0.005) upon SOD addition. These data demonstrate the feasibility of measuring both in vivo H2O2 and superoxide in the extracellular environment of human skeletal muscle, providing a technique with a potential application to a wide range of circulatory and metabolic studies of oxidative stress., J. D. La Favor, E. J. Anderson, R. C. Hickner., and Obsahuje bibliografii
Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting as early- onset mitochondrial encephalo- cardiomyopathies. Up to now, mutations in four nuclear genes were associated with isolated deficiency of ATP synthase. Two of them, ATP5A1 and ATP5E encode enzyme’s st ructural subunits α and ε , respectively, while the other two ATPAF2 and TMEM70 encode specific ancillary factors that facilitate the biogenesis of ATP synthase. All these defects share a similar biochemical phenotype with pronounced decrease in the content of fully assembled and functional ATP synthase complex. However, substantial differences can be found in their frequency, molecular mechanism of pathogenesis, clinical manifestation as well as the course of the disease progression. While for TMEM70 the number of reported patients as well as spectrum of the mutations is steadily increasing, mutations in ATP5A1, ATP5E and ATPAF2 genes are very rare. Apparently, TMEM70 gene is highly prone to mutagenesis and this type of a rare mitochondrial disease has a rather frequent incidence. Here we present overview of individual reported cases of nuclear mutations in ATP synthase and discuss, how their analysis can improve our understanding of the enzyme biogenesis., K. Hejzlarová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Osteoporosis is a systemic disease of the skeleton, characterized by reduction of bone mass and concurrent deterioration of bone structure. Consequently, bones are more fragile, and there is increased risk of fractures. The potential for acquisition of maximum bone mass is influenced by a number of factors. Among those are heredity, sex, nutrition, endocrine factors, mechanical influences and some risk factors. The best documented nutrient for metabolism of bone is calcium. Major role in the pathogenesis of osteoporosis have some micro and macro nutrients, prebiotics, alcohol, alternative diets, starvation and anorexia. Meta analysis of 29 randomized trials showed that supplementation with calcium and vitamin D3 reduces risk of bone fractures by 24 % and significantly reduces loss of bone mass. Osteoporosis has multi factor etiology. Osteoporosis is one of diseases which are influenced by nutrition and life style. It is preventable by means of adequate nutrition and sufficient physical activity., M. Stránský, L. Ryšavá., and Obsahuje seznam literatury
The aim of the study was to assess the association between promoter polymorphism [A(-596)G] in interleukin-6 gene and office systolic and diastolic blood pressures, and the heart rate (HR) in apparently healthy Czech subjects. Furthermore, we evaluated the possible influence of gender, BMI and smoking on these supposed associations. An age-matched (40-50 years) and gender-matched (F/M=81/89) sample of apparently healthy Czech subjects (n=170, F/M=81/89) without hypertension, other cardiovascular diseases or diabetes was examined. The A(-596)G Il-6 gene polymorphism was detected by the PCR method. No differences in genotype distribution and/or allelic frequency was found between groups with lower systolic blood pressure (£ 122 mm Hg) and higher systolic blood pressure (> 122 mm Hg). Similarly, no differences in the IL-6 polymorphism were found between lower (£ 86 mm Hg) and higher (> 86 mm Hg) diastolic blood pressure groups. However, we proved a significant increase of genotypes AG+GG as well as the allele (-596)G in higher (>78 beats/min) heart rate group. The genotypes AG+GG represent significantly higher relative risk for higher HR frequency, especially in women. Among lean persons with a low heart rate frequency, fewer AG+GG genotypes were determined than among any other subjects. The genotypes AG+GG are more frequent in non-smoking persons with higher HR compared to non-smoking subjects with lower HR, especially in women. Gender, BMI and smoking substantially modify the distribution of A(-596)G Il-6 gene polymorphism in apparently healthy persons with lower or higher heart rate., A. Vašků, M. Souček, M. Goldbergová, J. Vácha., and Obsahuje bibliografii
In this study we analyzed the effects of melatonin (Mel, 1 mg/kg ip) on behavioral changes as well as cell and oxidative damage prompted by bilaterally olfactory bulbectomy. Olfactory bulbectomy caused an increase in lipid peroxidation products and caspase-3, whereas it prompted a decrease of reduced glutathione (GSH) content and antioxidative enzymes activities. Additionally, olfactory bulbectomy induced behavioral changes characterized by the enhancement of immobility time in the forced swim test and hyperactivity in the open field test. All these changes were normalized by treatment of Mel (14 days). Our data show that Mel has a beneficial neuropsychiatric action against oxidative stress, cell damage and behavior alterations., I. Tasset ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
There is a large body of evidence documenting the effects of long-chain polyunsaturated fatty acids with the first double bond at the third position from methyl-terminal (so called omega-3 fatty acids (FAs)) on different components of cardiovascular disease (CVD) risk. However, it may seem the more answers on the topic we learn, the more questions remain to be elucidated. There are three levels of evidence documenting the impact of fish omega-3 FAs on CVD risk. Epidemiological data have shown unequivocally the increased intake of fish is associated with lower CVD morbidity and mortality. Numerous experimental studies have shown (almost always) positive effects of omega-3 FAs on lipoprotein metabolism, coagulation and platelet function, endothelial function, arterial stiffness etc. Most importantly, there are a few prospective clinical endpoint trials (DART, JELIS, GISSI Prevenzione and GISSI-HF) that have examined the impact of omega-3 FAs supplementation on cardiovascular outcomes in different patient populations. Recent meta-analyses of these and other clinical studies have yielded somewhat conflicting results. In this review we will summarize current evidence of omega-3 FAs effects on cardiovascular risk focusing on new data from recent clinical trials as well as possible practical implications for clinical practice., M. Vrablík ... [et al.]., and Obsahuje seznam literatury
Ongoing interest in brain ischemia research has provided data showing that ischemia may be involved in the pathogenesis of Alzheimer disease. Brain ischemia in the rat produces a stereotyped pattern of selectiv e neuronal degeneration, which mimics early Alzheimer disease pathology. The objective of this study was to further develop an d characterize cardiac arrest model in rats, which provides practical way to analyze Alzheimer- type neurodegeneration. Rats were made ischemic by cardiac arrest. Blood-brain barrier (BBB) insufficiency, accumulation of different parts of amyloid precursor protein (APP) and platelets inside and outside BBB vessels were investigated in ischemic brain up to 1-year survival. Isch emic brain tissue demonstrated haphazard BBB changes. Toxic fr agments of APP deposits were associated with the BBB vessels. Moreover our study revealed platelet aggregates in- and outside BBB vessels. Toxic parts of APP and platelet aggregates correlated very well with BBB permeability. Progressive injury of the ischemic brain parenchyma may be caused not only by a degeneration of neurons destroyed during ischemia but also by chronic damage in BBB. Chronic ischemic BBB insufficiency with accumulation of toxic components of APP in the brain tissue perivascular space, may gradually over a lifetime, progress to brain atrophy and to full blown Alzheimer-type pathology., M. Jabłoński., and Obsahuje bibliografii a bibliografické odkazy