A daily rhythm in the oscillations of pineal dopamine, norepinephrine and epinephrine content was found in male Wistar:Han rats. The acrophases of the oscillations were localized in the first half of the dark period and generally higher values were found in the dark part of the day., I. Ahlers, B. Pástorová, P. Solár, E. Ahlersová., and Obsahuje bibliografii
The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) which is widely used in agriculture is known to cause dopaminergic neurotoxicity. However, the mechanisms underlying this effect are not fully understood. This present study investigated the behavioral manifestations, motor coordination, and dopaminergic neurodegeneration following exposure to PQ. Male rats were injected with PQ (10 mg/kg i.p.) daily for three weeks. Rotarod systems were used for measuring locomotor activity and motor coordination. The effects of PQ on dorsiflexor, electrophysiologically-induced muscle contraction were studied. Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. PQ induced difficulty in movement and significant reduction in motor activity and twitch tension at the dorsiflexor skeletal muscle. The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4±3.4 pg/mg) when compared with control animals (55.0±2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia nigra and significant behavioral and peripheral motor deficit effects., M. A. Fahim, ... [et al.]., and Obsahuje seznam literatury
A theoretical model is presented, which attempts to account for the evaluation of complex stimuli in terms of their constituent elements that are relevant to the intent of the assessment. The subjective evaluation of a compound stimulus is postulated to be a function of the number, weight and integrity of critical components, or sub-qualities, and their interactions. The model has application to the evaluation of any stimulus complex including works of “art”. For illustrative purpose, it will here be applied to the analysis of pictorial works of art., J. P. Huston., and Obsahuje bibliografii
This work discusses the clinical performance of deconjugated metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) determined in the basal first morning urine using a chromatographic method with electrochemical detection for the clinical diagnosis of pheochromocytoma (PHEO) and paraganglioma (PGL). Urine samples were collected from 44 patients (36 with PHEO, 8 with PGL) aged 54+/-17 (20-78) years (22 females, 22 males). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The control group consisted of 34 PHEO/PGL patients more than 4 months after adrenal gland surgery. All subjects in the control group were without a diagnosis of PHEO or PGL. Clinical sensitivity was 55 % for MN, 64 % for NMN, 80 % for combination of both MN and NMN, and only 23 % for 3TM. Clinical specificity calculated from the control group was 93 % for MN, 95 % for NMN, 95 % for the combination MN and NMN, and 97 % for 3TM. Cut-off values for deconjugated metanephrines in the basal urine were 310 (MN), 690 (NMN) and 250 μg/l (3MT). Chromatographic determination of deconjugated urinary metanephrines, which is simple without the necessity of special laboratory material, can serve for the screening of PHEO or PGL patients. Urine NMN and 3MT exerts an association to malignity, and all markers are associated with tumor mass. However, the principal laboratory diagnosis of PHEO or PGL must be based on plasma-free metanephrines and plasma chromogranin A with better performance in the laboratory diagnosis of PHEO or PGL., R. Bílek, T. Zelinka, P. Vlček, J. Dušková, D. Michalský, K. novák, J. Bešťák, J. Widimský Jr., and Obsahuje bibliografii
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
Matriptase-2, a membrane protein encoded by the Tmprss6 gene, is a negative regulator of hepcidin expression. Although matriptase-2 has been proposed to cleave membrane hemojuvelin, we have recently found decreased hemojuvelin protein levels in Tmprss6 -/- mice. The purpose of this study was to confirm this observation by determining hemojuvelin protein levels in another strain of mice with disrupted Tmprss6 gene, and to determine the effect of matriptase-2 deficiency on the expression of other membrane proteins participating in the bone morphogenetic protein signal transduction. Mask mice, which lack the proteolytic domain of matriptase-2, displayed decreased liver hemojuvelin protein content, while Id1 mRNA level, an indicator of hemojuvelin-dependent signal transduction, was increased. Protein levels of bone morphogenetic protein receptors Alk3 and Acvr2a were unchanged, and tran sferrin receptor 2 and neogenin protein levels were slightly decreased. The results confirm that the loss of matriptase-2 increases bone morphogenetic protein- dependent signaling, while pa radoxically decreasing liver hemojuvelin protein content. The regulation of transferrin receptor 2 protein levels by transferrin saturation was not affected in mask mice. How the loss of matriptase-2 proteolytic activity leads to decreased hemojuvelin protein levels is at present unclear., J. Frýdlová, ... [et al.]., and Obsahuje seznam literatury
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
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
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
Dehydroepiandrosterone (DHEA) and its sulphate-bound form (DHEAS) are important steroids mainly of adrenal origin. Their physiological and pathophysiological functions are not yet fully identified, although a number of various possible features have been hypothesized. Most popular is the description of the “hormone of youth” as the long-term dynamics of DHEA levels are characterized by a sharp age-related decline in the late adulthood and later. Low levels of DHEA are, however, associated not only with the ageing process but also with diabetes mellitus, cardiovascular diseases and some neurological or immunological entities. In the past decade, a number of brief studies have concentrated on these relationships and also on the role of exogenous DHEA in health, disease and human well-being. This article tries to summarize some of the most important facts achieved recently., P. Celec, L. Stárka., and Obsahuje bibliografii