Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA., O. Sglunda, H. F. Mann, H. Hulejová, O. Pecha, L. Pleštilová, O. Růžičková, M. Fojtíková, O. Šléglová, Š. Forejtová, K. Pavelka, J. Vencovský, L. Šenolt., and Obsahuje bibliografii
Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an associatio n of esRAGE and methylglyoxal- adducts serum level, as well as AGE-to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipidemia and macrovascular disease in history. In diabetes with concomitant hyperlipidemia esRAGE was significantly decreased compared to hyperlipidemia with normal glucose metabolism (0.306±0.2 vs. 0.367± 0.1; p=0.019) or diabetes alone (0.306±0.2 vs. 0.404±0.1; p = 0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipidemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was re cognized as a high risk for vascular disease outcomes., Z. Turk, S. Ljubić, J. Boras., and Obsahuje bibliografii a bibliografické odkazy
Cíl: Cílem práce je charakterizovat klinické a elektrofyziologické nálezy dvou typů ulceromutilující dědičné neuropatie CMT2B a HSN1 u tří českých rodin s molekulárně geneticky objasněnou příčinou. Soubor: Popisujeme tři rodiny s dědičnou senzitivní neuropatií s celkem 16 postiženými. Metodika: Na základě neurologického a elektromyografického vyšetření, výskytu podobných obtíží u příbuzných byla stanovena diagnóza senzitivní, převážně axonální neuropatie. Následně bylo provedeno sekvenování genů SPTLC1 a RAB7 v rodinách A, B, C a u dalších 24 nepříbuzných pacientů s klinickým podezřením na dědičnou senzitivní neuropatii. Výsledky: V rodině B byla nálezem mutace p.C133Y v SPTLC1 genu prokázána hereditární senzitivní neuropatie typ 1 (HSN1). V rodinách A a C byla nálezem mutací p.L129F a p.V162M v genu RAB7 prokázána choroba Charcot‑Marie‑Tooth typ 2B (CMT2B). Všechny tři mutace již byly dříve popsány a fenotyp odpovídá popisu pacientů z jiných zemí. DNA vyšetření dalších 24 nepříbuzných pacientů však příčinu onemocnění neobjasnilo. Závěr: Ulceromutilující dědičné neuropatie CMT2B a HSN1 jsou v české populaci, podobně jako v jiných zemích vzácné, ale klinické projevy jsou jasně poznatelné, pokud jsou zohledněny a správně získány genealogické údaje – rodinná anamnéza. Tyto tři popsané rodiny jsou dosud jediné známé v ČR s objasněnou příčinou dědičné senzitivní neuropatie v důsledku mutací v RAB7 a SPTLC1. Objasnění příčiny ulceromutilující senzitivní neuropatie má význam nejen pro upřesnění genetické a klinické prognózy a pro cílenou genetickou prevenci, ale u pacientů s mutacemi v SPTLC1 genu možná i pro cílenou terapii se substitucí L‑serinem, která bude testována v klinické studii (Boston, USA), Aim: The goal was to clinically and electrophysiologically characterize two types of ulceromutilating hereditary neuropathy CMT2B and HSN1 in three Czech families where molecular genetic cause was confirmed. Patients: We describe three families, overall 16 affected patients, with hereditary sensory neuropathy. Methods: The diagnosis of sensory, predominantly axonal neuropathy was done on the basis of neurological and electrophysiological examination. Sequencing of the SPTLC1 and RAB7 genes was done in families A, B, C and 24 unrelated patients with clinical suspicion for HSN. Results: Hereditary sensory neuropathy type 1 (HSN1) caused by the p.C133Y mutation in the SPTLC1 gene was confirmed in family B and the Charcot-Marie-Tooth type 2B (CMT2B) caused by p.L129F and p.V162M mutations in the RAB7 gene was confirmed in families A and C. All three mutations have been previously described. DNA examination of 24 unrelated patients did not reveal the cause of their disease. Conclusion: As in other countries, ulceromutilating hereditary neuropathies CMT2B and HSN1 are rare in the Czech population. However, clinical manifestations are clearly recognizable if correctly obtained genealogical data – family history – is properly taken into account. The three families described here are the only known families with hereditary neuropathies caused by mutations in RAB7 and SPTLC1 in the Czech Republic. Clarification of the cause of ulceromutilating sensory neuropathy is crucial for genetic and clinical prognosis, including targeted genetic prevention, but possibly also for an L-serin therapy in SPTLC1 mutation patients to be tested in a clinical study (Boston, USA)., and D. Šafka Brožková, R. Mazanec, J. Böhm, O. Vyšata, M. Auer-Grumbach, Ch. Windpassinger, J. Neupauerová, L. Baránková, S. Nevšímalová, P. Seeman
INTRODUCTION: Cellulitis remains a very serious disease even today. Mortality, which varied between 10-40%, has been reduced owing to the standard securing of airway patency and use of an appropriate surgical treatment approach. MATERIALS AND METHODS: A total of 195 patients were hospitalised for cellulitis at the University Hospital in Hradec Králové during 2007-2011. The following parameters were evaluated: age, gender, dependence of incidence of the disease on the season of the year, frequency of attacks of the particular areas and their clinical characteristics, aetiology of the inflammation, types of patient complaints, prevalence of current systemic diseases, results of microbiological and selected laboratory analyses, socio-economic status of the patients, and duration of patient stay at the hospital. Statistical analysis was performed by using Pearson's correlation coefficient, the statistical significance level was p < 0.05. RESULTS: The mean age of the patients was 39.8 years. The group of 195 patients included 108 (55%) males and 87 (45%) females. The mean time between the first symptoms of the disease and admission to the Department was 5 days. From among the 195 patients, 116 (59.5%) were working persons, 79 (40.5%) were non-working (children, students, unemployed persons, women on maternity leave, retired people). The odontogenic origin of the disease was verified in 173 (88.7%) patients. In total, 65 (33.3%) patients had no coinciding complicating systemic disease, 22 (11.3%) patients had diabetes mellitus. The most frequent symptom of cellulitis was painful swelling, found in 194 (99.5%) patients, followed by jaw contracture, found in 153 (78.5%) patients. CONCLUSION: The results are largely very similar to those of previous studies performed in other countries, except that we found no correlation between the prevalence of cellulitis and the socio-economic status, nor have we confirmed Klebsiella pneumoniae sp. as the cause of cellulitis in patients with diabetes mellitus. and H. Doležalová, J. Zemek, L. Tuček
Abnormal release of Ca2+ from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction in heart failure (HF). We previously demonstrated that RyR2 macromol ecular complexes from HF rat were significantly more depleted of FK506 binding protein (FKBP12.6). Here we assess ed expression of key Ca2+ handling proteins and measured SR Ca2+ content in control and HF rat myocytes. Direct measurements of SR Ca2+ content in permeabilized cardiac myocytes demonstrated that SR luminal [Ca2+] is markedly lowered in HF (HF: Δ F / F 0 = 26.4±1.8, n =12; control: Δ F / F 0 = 49.2±2.9, n =10; P <0.01). Furthermore, we demonstrated that the expression of RyR2 associated proteins (including calmodulin, sorcin, calsequestrin, protein phosphatase 1, protein phosphatase 2A), Ca2+ ATPase (SERCA2a), PLB phosphorylation at Ser16 (PLB-S16), PLB phosphorylation at Thr17 (PLB-T17), L-type Ca 2+ channel (Cav1.2) and Na+-Ca 2+ exchanger (NCX) were significantl y reduced in rat HF. Our results suggest that systolic SR reduced Ca2+ release and diastolic SR Ca2+ leak (due to defective protein-protein interaction between RyR2 and its associated proteins) along with reduced SR Ca2+ uptake (due to down-regulation of SERCA2a, PLB-S16 and PLB- T17), abnormal Ca2+ extrusion (due to down-regulation of NCX) and defective Ca2+-induced Ca2+ release (due to down-regulation of Cav1.2) could co ntribute to HF., S.-T. Hu., and Obsahuje bibliografii a bibliografické odkazy
Administrative courts at the onset of the new century face the challenge of ever-changing legislation. Frequent amendments do solvee some gaps but creat even more gaps which have to be filled by the courts. in the CZech Republic relative ease of judicial review by the courts of first instance and the wide open access to the Supreme Administrative Court mean that many administrative cases are resolved in four instances - two instances of administrative proceedings and additional two instances of judicial proceedings. All these things considered, it is not surprising that neither legal scholarship nor case law defines any general concept of judicial deference (or self-restraint) to the administration. Various areas of public law contain some expressions of judicial deference (most notably the limitation of judicial review of administrative discretion and subsidiarity of judicial review). Nevertheless, both case law and scholarship are far from subsuming these concepts under the common label of "judicial deference to the administration". This paper provides an in-depth analysis of the notion of judicial deference in the Czech Republic as well as some prospects in this field., Zdenek Kühn, Josef Staša., and Obsahuje bibliografické odkazy
Mitochondrial dysfunction and oxidative stress participate in the development of diabetic complications, however, the mechanisms of their origin are not entirely clear. Coenzyme Q has an important function in mitochondrial bioenergetics and is also a powerful antioxidant. Coenzyme Q (CoQ) regenerates alpha-tocopherol to its active form and prevents atherogenesis by protecting low-density lipoproteins against oxidation. The aim of this study was to ascertain whether the experimentally induced diabetes mellitus is associated with changes in the content of endogenous antioxidants (alpha-tocopherol, coenzymes Q9 and Q10) and in the intensity of lipoperoxidation. These biochemical parameters were investigated in the blood and in the isolated heart and liver mitochondria. Diabetes was induced in male Wistar rats by a single intravenous injection of streptozotocin (45 mg.kg-1), insulin was administered once a day for 8 weeks (6 U.kg-1). The concentrations of glucose, cholesterol, alpha-tocopherol and CoQ homologues in the blood of the diabetic rats were increased. The CoQ9/cholesterol ratio was reduced. In heart and liver mitochondria of the diabetic rats we found an increased concentration of alpha-tocopherol, however, the concentrations of CoQ9 and CoQ10 were decreased. The formation of malondialdehyde was enhanced in the plasma and heart mitochondria. The results have demonstrated that experimental diabetes is associated with increased lipoperoxidation, in spite of the increased blood concentrations of antioxidants alpha-tocopherol and CoQ. These changes may be associated with disturbances of lipid metabolism in diabetic rats. An important finding is that heart and liver mitochondria from the diabetic rats contain less CoQ9 and CoQ10 in comparison with the controls. We suppose that the deficit of coenzyme Q can participate in disturbances of mitochondrial energy metabolism of diabetic animals., J. Kucharská, Z. Braunová, O. Uličná, L. Zlatoš, A. Gvozdjáková., and Obsahuje bibliografii
The article deals with estimating deformation between the African and the Eurasian Plate in the Eastern Mediterranean on the basis of GPS coordinate time series. Two sources of velocities were used for processing. The first was the freely available site velocities from the European Permanent Network (EPN). The second was the Egyptian GPS permanent network velocities. Their values were determined by the following technique. Firstly, the Egyptian site coordinates were computed from GPS daily observations, using the fiducial EPN stations. The daily site coordinates at a given time interval result in coordinate time series, which were analysed and used on velocity estimation of the Egyptian stations. Then the apparatus of the mechanics of continuum was applied to all resultant velocities. The regions of possible mutual interactions between the Eurasian and the African Plate in the Eastern Mediterranean were detected. The basic idea of this contribution is the common processing of GPS daily measurements from the Egyptian permanent network together with the EPN data. The available Egyptian GPS data cover almost the last three years, which represents a sufficient time interval for velocity estimation. Introducing the Egyptian permanent GPS measurements into processing enables a better estimate of deformations in the Eastern Mediterranean., Antonín Zeman, Khalil Hassan, Jan Holešovský, Abdel Monem S. Mohamed, Zbyněk Novotný, Mahmoud M. Salah, Jan Kostelecký and Radwan M. Ali., and Obsahuje bibliografii
Brown coal open pit mining in the basin under Krušné Hory Mts. came to contact with slopes of the mountains, and a problem of the stability in high and steep slopes in the crystalline rock became an important question. The question concerns Jezeří Castle built on the top of one of the hills in a most endangered section where even a supporting pillar in the sediments under the slope toe was left to support the slope. As a result, an extensive monitoring program regarding deformations was initiated in the region. The program involved several methods and some important results are discussed. The results that are displayed concern mainly measurements done in geophysical tiltmeter stations in two underground galleries driven into the two steep slope sections showing most dangerous situation, as well as extensometers located in the same locations. Long-term monitoring revealed a tectonic deformation process of a natural origin that is registered as slow and systematic tilts. Besides, it revealed several periods of anomalies that are of basic importance. During a long period of observation from 1982 till 2005 three important deformation anomalies were registered: the event of 1994, the event of 2002, and the event of 2003/2004. The first and the third event have been classified as of a large regional character that affected a wide mountainous area and could be interpreted as a tectonic impulse originating within the mountainous structure of the so called "Dome of Hora Svaté Kateřiny". The second event has been considered different, strictly connected with extreme precipitation of August 2002. The anomaly was evidenced even deep in the crystalline, so that it could not be seen as of a superficial character only. The movement which was registered at that time was oriented right into the pillar supporting the slope., It is concluded that it was a short manifestation of instability in the critical profile "Jezeří - pillar", which stresses the important stabilisation function of the supporting pillar without which the profile will be probably destabilised., Blahoslav Košťák, Bohumil Chán and Jan Rybář., and Obsahuje bibliografii
This paper is devoted to the study of matrix elements of irreducible representations of the enveloping deformed Heisenberg algebra with reflection, motivated by recurrence relations satisfied by hypergeometric functions. It is shown that the matrix elements of a suitable operator given as a product of exponential functions are expressed in terms of d-orthogonal polynomials, which are reduced to the orthogonal Meixner polynomials when d = 1. The underlying algebraic framework allowed a systematic derivation of the recurrence relations, difference equation, lowering and rising operators and generating functions which these polynomials satisfy., Fethi Bouzeffour, Hanen Ben Mansour, Ali Zaghouani., and Obsahuje bibliografii