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
Compression of the rostral ventrolateral medulla oblongata (RVLM) by an abnormally located artery is regarded as one possible cause of arterial hypertension. There exists a limited set of data suggesting that increased sympathetic activity in patients with RVLM compression may lead to arterial hypertension. Accordingly, we decided to assess the sympathetic activity in patients with severe arterial hy pertension and to investigate any correlation with the presence of RVLM compression. Sixty-four patients with severe arterial hypertension were enrolled in our study. Sympathetic activity was evaluated using 24-hour urinary norepinephrine as measured by high-pressure liquid chromatography with electrochemical detection. The presence of RVLM compression was assessed with magnetic resonance imaging. Neurovascular compression of the RVLM was identified in 40 patients, 27 of whom presented left-sided compression. Twenty-four hour urinary norepinephrine averaged 263.6± 135.9 nmol in patients with neurovascular compression - 255.6±137.3 nmol in those with left-sided compression and 251.6±138.5 nmol in patients without RVLM compression. We did not identify any increase in urinary norepinephrine in patients with severe arterial hypertension and neurovascular compression of the RVLM. Our results do not support the hypothesis that neurovascular compression of RVLM may exhibit a sympathetically mediated increase in blood pressure., M. Solař ... [et al.]., and Obsahuje seznam literatury
Pulse dye densitometry (PDD) enables the evaluation of hemodynamic state as well as liver function. A repeated examination, even after a short pause (or under stress condition), enables to follow safely the dynamics of liver pathology. From presented parameters we have evaluated as reliable the C5-clearance, an expression of equilibrium state in the two compartment liver system. Furthermore, T-index expresses ratio of C5 value to cardiac output, it is a sensitive indicator of the blood pole, i.e. sinusoidal uptake, which is in very good correlation with staging of hepatopathies. The isolated h constant in correlation to T-index is valuable For functional grading. The Japanese automatic analyzer of indocyanine green (ICG) dilution and elimination curves, after incorporation of a two compartment mathematical mode l, becomes more useful for complex hepatological diagnostics. Non-invasive PDD is becoming of uppermost importance to clinic al interest, yielding comparable results as other complicated and invasive examinations and may be, therefore, repeated in short time intervals for different indications with minimal stress of examined patient., J. A. Tichý ... [et al.]., and Obsahuje seznam literatury
Our present focus on the hypoxic immature heart is driven by clinical urgency: cyanotic congenital cardiac malformations remain the single largest cause of mortality from congenital defects and ischemic heart disease is no more the disease of the fifth and older decades but its origin as well as risk factors are present already during early ontogeny. Moreover, the number of adult patients operated for cyanotic congenital heart disease during infancy steadily increases. This group approaches the age of the rising risk of serious cardiovascular diseases, particularly ischemic heart disease. Experimental results have clearly shown that the immature heart is significantly more tolerant to oxygen deficiency than the adult myocardium. However, the mechanisms of this difference have not yet been satisfactorily clarified; they are likely the result of developmental changes in cardiac energy metabolism, including mitochondrial function. The high resistance of the newborn heart cannot be further increased by ischemic preconditioning or adaptation to chronic hypoxia; these protective mechanisms appear only with decreasing tolerance during development. Resistance of the adult myocardium to acute oxygen deprivation may be significantly influenced by perinatal hypoxia. These results suggest that the developmental approach offers new possibilities in the studies of pathogenesis, prevention and therapy of critical cardiovascular diseases., B. Ošťádal ... [et al.]., and Obsahuje seznam literatury
The effect of oral supplementation with glycosaminoglycans (GAG) and radical scavengers (vitamin E/selenium) on the regeneration of osteochondral defects was investigated in rabbits. After introduction of defined osteochondral defects in the knee joint, groups of ten animals were given a GAG/vitamin E/selenium mixture or a placebo (milk sugar) for 6 weeks. Following sacrifice, histological and histochemical analysis was performed. The amount of synovial fluid was increased in the placebo group, while the viscosity of the synovial fluid was significantly enhanced in the GAG group. The amount of sulfated GAG in the osteochondral regenerates (8.8±3.6 % vs. 6.0±5.6 %; p<0.03) was significantly higher in the GAG group. In both groups, the GAG amount in the cartilage of the operated knee was significantly higher than in the non-involved knee (p<0.05). Histological analysis of the regenerates in the GAG group was superior in comparison with the placebo group. For the first time, a biological effect following oral supplementation with GAG was demonstrated in healing of osteochondral defects in vivo. These findings support the known positive clinical results., M. Handl, E. Amler, K. Bräun, J. Holzheu, T. Trč, A. B. Imhoff, A. Lytvynets, E. Filová, H. Kolářová, A. Kotyk, V. Martínek., and Obsahuje bibliografii a bibliografické odkazy