The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing’s syndrome. Twenty-nine patients with active Cushing’s syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-β-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8±74.2 vs. 210.9±56.3 ng.ml-1, p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3±13.0 vs. 63.3±32.4 PU, p<0.01, and 90.4±36.6 vs. 159.2±95.3 PU, p<0.05, respectively ) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2±1.5 vs. 5.2±3.4 PU.s-1, p<0.05, and 0.95±0.6 vs. 1.8±1.1 PU.s-1, p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus., M. Prázný, J. Ježková, E. Horová, V. Lazárová, V. Hána, J. Kvasnička, L. Pecen, J. Marek, J. Škrha, M. Kršek., and Obsahuje bibliografii a bibliografické odkazy
In healthy subjects, the right ventricular filling pattern estimated from tricuspid valve inflow is highly load-dependent. This can be clearly demonstrated by changes of Doppler inflow tracings recorded during tidal breathing at rest. The aim of our study was to test the magnitude of tricuspid inflow changes during more pronounced load changes induced by specific maneuvers. In 31 apparently healthy subjects (16 men and 15 women, mean age 36±16 years) we recorded pulsed Doppler tracings of tricuspid inflow during forced inspiration, elevation of lower extremities (increased preload) and handgrip exercise (increased afterload). The obtained values were compared with end-expiratory phase of tidal breathing at rest. We found a significantly larger increase in the early and late filling velocities (for E and A p<0.001) under the conditions of increasing preload (elevation of legs) and less pronounced, but still significant changes with isometric exercise (for E p<0.001 and for A p<0.01). We conclude that the right ventricular filling pattern in healthy humans is highly load-sensitive and for this reason the effect of any intervention (e.g. pharmacological) must be studied under strict and well-defined resting conditions., E. Mandysová, P. Niederle., and Obsahuje bibliografii a bibliografické odkazy
Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin., I. Matějovská, K. Bernášková, D. Krýsl, J. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Huntington’s disease (HD) is a demential, neurodegenerative inheritable disease affecting middle-aged patients. HD is characterized by uncontrolled choreiform movements, psychiatric symptoms and cognitive decline. Histopathological changes in HD brains reveal a considerable damage to basal ganglia, particularly affecting middle-sized spiny neurons from the caudate-putamen region. Neurochemical changes are specifically oriented to deplete GABAergic and cholinergic systems, while molecular alterations include an increased expression of CAG trinucleotide at exon 1 from the huntingtin (htt) gene, as well as aggregation of mutant htt. Although several hypotheses regarding the mechanisms by which neurotoxicity is triggered in HD brains have been suggested on the basis of experimental evidence, so far it remains not clear which of them are predominant or whether they are complementary. Recent experimental evidence through transgenic mice models reveal an interesting inter action between expanded CAG triplets, mutant htt, and the increase in toxic metabolites from the kynurenine pathway. Further evidence supports the assumption that different toxic mechanisms (i.e. excitotoxicity, energy metabolism impairment, inflammatory events, oxidative stress, etc.) are confluent and depend on each other. In this review we will briefly summarize some of those findings and propose a final integrative hypothesis for HD., V. Pérez-de la Cruz, A. Santamaría., and Obsahuje bibliografii a bibliografické odkazy
Proteinuria has been recently shown to be an independent risk factor for the progression of chronic nephropathies, but the actual mechanisms by which urinary protein load damages renal tissue in humans remain unsolved. Using real-time RT-PCR method we evaluated intrarenal mRNA expression of various cytokines and chemokines in patients with biopsy-proven IgA nephropathy (IgAN, n=11), membranous nephropathy (MN, n=6) and focal and segmental glomerulosclerosis (FSGS, n=6) who exhibited proteinuria over 0.5 g/day. There was a significant positive correlation between the proteinuria extent and the intrarenal RANTES (regulated upon activation normal T cell expressed and secreted) mRNA expression in patients with IgAN, a similar trend was also observed in patients with MN and FSGS. There were no clear relationships between the proteinuria and intrarenal mRNA expression of tumor necrosis factor α, transforming growth factor β1 and monocyte chemoattractant peptide-1. There were no differences in the pattern of cytokine mRNA expression between different glomerulopathies. In conclusion, our results support the hypothesis that lymphocytes, macrophages and their products provoke tissue in jury in response to proteinuria independently of the nature of renal diseases in man., I. Brabcová, K. Kotsch, P. Hřibová, A. Loužecká, K. Bartošová, K. Hyklová, J. Lácha, H.-D. Volk, O. Viklický., and Obsahuje bibliografii a bibliografické odkazy
Leptin is a hormone that regulates food intake. During inflammatory status, leptin may contribute to the anorexia and cachexia of infection. Pulmonary endarterectomy was used as a model of non-infectious cytokine network hyperstimulation. Leptin and soluble leptin receptor (SLR) were compared with evolution of cortisol and inflammatory cytokines in twenty-two patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy using cardiopulmonary bypass (CBP) and deep hypothermic circulatory arrest (DHCA). Leptin, SLR, cortisol, IL-1β, IL-6, IL-8, and TNFα concentrations in arterial blood were measured before/after sternotomy, last DHCA, separation from bypass, 12, 18, 24, 36, and 48 h after sternotomy. Mean duration of CPB was 338.2 min.; mean circulatory arrest time 39.9 min. The initial decline of leptin, SLR, TNFα, IL-6, and IL-8 was followed by an increase culminating 6-24 h after sternotomy. Leptin peak levels were detected 24 h after sternotomy (28.0 ng/ml, 21.9-37.6). IL-6 culminated after separation from CPB, IL-8 was highest 12 h after sternotomy. Leptin concentrations correlated with IL-6 (r=0.82), and TNFα (r=0.73). Large cardiovascular surgery caused a significant increase in serum leptin, indicating its acute regulation by stress factors. This effect may be secondary to the inflammatory response mediated via cytokine stimulation. Correlation between leptin and IL-6 indicates the role of IL-6 in leptin induction., P. Maruna, J. Lindner, K. M. Kubzová., and Obsahuje seznam literatury
More than 50 % of end-stage renal disease (ESRD) patients treated by chronic hemodialysis die from cardiovascular diseases, including congestive heart failure (CHF). The incidence of CHF is rising in both general and ESRD population. However, the mechanisms, which lead to the development of CHF in dialyzed patients, differ considerably. First, there are several factors leading to increase of the left ventricular afterload: volume overload between dialyses, hypertension, increased arterial stiffness, anemia, vascular access flow (arteriovenous fistula) and sympathetic activation. Second, hypertension, left ventricular hypertrophy, anemia and frequently present coronary artery disease worsen myocardial oxygenation. The combination of these factors explains the high incidence of CHF in dialyzed patients and their roles are reviewed in this article., J. Malík ... [et al.]., and Obsahuje seznam literatury
Epilepsie je složité neurologické onemocnění s mnoha projevy, jímž v České republice trpí na 80 tisíc lidí; v celosvětovém měřítku se toto číslo pohybuje kolem neuvěřitelných 50 milionů. V řadě případů je příčina neznámá. Pacienty však netrápí jen sama choroba a její příznaky - což nemusí být pouze záchvaty, ale také další projevy včetně úzkostí, deprese, poruch paměti, pozornosti, chování atd. Život jim ztěžuje též určitá stigmatizace, jelikož společnost stále ještě vnímá toto onemocnění značně nepříznivě. and Jana Olivová.