Acute lung injury occurs mostly in the very low birth weight and extremely low birth weight infants. The pathological process leading to acute lung injury includes immature and/or diseased lung that experienced oxidative stress, inflammation and mechanical insult with the bronchial, alveolar and capillary injuries and cell death. It may be the first step to the subsequent development of chronic lung disease of prematurity or bronchopulmonary dysplasia. The mechanisms of lung injury are extensively investigated in the experimental models and clinical studies, mostly performed on the adult patients. At present, the explanations of the mechanism(s) leading to lung tissue injury in tiny premature babies are just derived from these studies. Acute lung injury seems to be rather a syndrome than a well-defined nosological unit and is of multifactorial etiology. The purpose of this review is to discuss the main factors contributing to the development of acute lung injury in the very low or extremely low birth weight infants - lung immaturity, mechanical injury, oxidative stress and inflammation. Nevertheless, numerous other factors may influence the status of immature lung after delivery., P. Zoban, M. Černý., and Obsahuje bibliografii
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
Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain., S. Poništ, L. Slovák, V. Kuncírová, T. Fedorova, A. Logvinenko, O. Muzychuk, D. Mihalová, K. Bauerová., and Obsahuje bibliografii
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
As traditional risk factors are unable to fully explain the pathogenesis of coronary artery disease (CAD), novel mechanisms became a target of many investigations. Our aim was to study the response of selected markers to physical exercise. High-sensitive C-reactive protein (hs-CRP), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), advanced oxidation protein products (AOPP), soluble receptor for advanced glycation end-products (sRAGE), pregnancy-associated plasma protein A (PAPP-A), E-selectin, vascular endothelial growth factor (VEGF) and B-type natriuretic peptide (BNP) levels were measured in serum of 21 CAD patients and in 22 healthy controls at rest and after exercise bicycle stress test performed up to the maximal tolerated effort. At rest, hs-CRP, AOPP, MMP-9 and BNP were significantly elevated in the CAD patients as compared with controls. In contrast, P-selectin was significantly lower in CAD patients and a tendency to lower levels of sRAGE was noted. After exercise MMP-9 and BNP, increased significantly in both groups. In conclusions, CAD patients have elevated hs-CRP, AOPP, MMP-9 and BNP - novel markers related to cardiovascular risk or left ventricular overload. MMP-9 and BNP increase significantly with exercise in both healthy individuals and CAD patients., V. Danzig ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A2 (mt-PLA2) have been previously suggested to be activated by ROS. Therefore, we have attempted to elucidate physiological role of such activation. We have found that function of a specific i-isoform of mitochondrial phospholipase A2 (mt-iPLA2) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA2 inhibitor. Concomitant uncoupling has been caused by free fatty acids, since it was inhibited by bovine serum albumin. The uncoupling was manifested as a respiration burst accompanied by a slight decrease in mitochondrial inner membrane potential. Since this uncoupling was sensitive to carboxyatractyloside and purine nucleotide di- and triphosphates, we conclude that it originated from the onset of fatty acid cycling mediated by the adenine nucleotide translocase (major contribution) and mitochondrial uncoupling protein(s) (minor contribution), respectively. Such a mild uncoupling may provide a feedback downregulation of oxidative stress, since it can further attenuate mitochondrial production of ROS. In conclusion, ROS-induced function of cardiac mt-iPLA2 may stand on a pro-survival side of ischemia-reperfusion injury., Ježek, J. ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The study aimed to evaluate if the monitoring of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipoperoxides (LPO) and interleukin-6 (IL-6) in plasma could help to predict development of diabetic complications (DC). Clinical and biochemical parameters including AGEs, AOPP, LPO and IL-6 were investigated in patients with type 2 diabetes mellitus (DM2) with (+DC) and without (-DC) complications. AGEs were significantly higher in both diabetic groups compared to controls. AGEs were also significantly higher in group +DC compared to -DC. AGEs significantly correlated with HbA1c. We observed significantly higher AOPP in both diabetic groups in comparison with controls, but the difference between -DC and +DC was not significant. LPO significantly correlated with BMI. IL-6 were significantly increased in both diabetic groups compared to controls, but the difference between -DC and +DC was not significant. There was no significant correlation between IL-6 and clinical and biochemical parameters. These results do not exclude the association between IL-6 and onset of DC. We suggest that the measurement of not only HbA1c, but also AGEs may be useful to predict the risk of DC development in clinical practice. Furthermore, the measurement of IL-6 should be studied as adjunct to HbA1c monitoring., V. Jakuš, E. Šándorová, J. Kalninová, B. Krahulec., and Obsahuje bibliografii
Hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play an important role in brain control of blood pressure (BP). One of the important mechanisms involved in the pathogenesis of hypertension is the elevation of reactive oxygen species (ROS) production by nicotine adenine dinucleotide phosphate (NADPH) oxidase. The aim of our present study was to investigate NADPH oxidase -mediated superoxide (O 2 - ) production and to search for the signs of lipid peroxidation in hypothalamus and medulla oblongata as well as in renal medulla and cortex of hypertensive male rats transgenic for the murine Ren -2 renin gene (Ren -2 TGR) and their age -matched normotensive controls ‒ Hannover Sprague Dawley rats (HanSD) . We found no difference in the activity of NADPH oxidase measured as a lucigenin -mediated O 2 - production in the hypothalamus and medulla oblongata. However, we observed significantly elevated NADPH oxidase in both renal cortex and medulla of Ren -2 TGR com pared with HanSD. Losartan (LOS) treatment (10 mg/kg body weight/day) for 2 months (Ren -2 TGR+LOS) did not change NADPH oxidase -dependent O 2 - production in the kidney. We detected significantly elevated indirect m arkers of lipid peroxidation measured as th iobarbituric acid -reactive substance s (TBARS) in Ren -2 TGR, while they were significantly decreased in Ren -2 TGR +LOS. In conclusion, the present study shows increased NADPH oxidase activities in renal cortex and medulla with significantly increased TBARS in renal cortex. No significant changes of NADPH oxidase and markers of lipid peroxidation were detected in the studied brain regions., M. Vokurková, H. Rauchová, L. Řezáčová, I. Vaněčková, J. Zicha., and Obsahuje bibliografii
The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition., S. B. Pajović, M. B. Radojčić, D. T. Kanazir., and Obsahuje bibliografii a bibliografické odkazy
The protective effect of therapeutic hypothermia in cardiac arrest survivors (CAS) has been previously well documented. Animal studies have indicated that attenuation of tissue oxidative stress (OS) may be involved in the mechanisms that lead to the beneficial effect of hypothermia. The extent of OS and nitric oxide (NO) production in adult CAS treated with endovascular hypothermia is, however, unknown. A total of 11 adult patients who experienced cardiac arrest out of hospital were included in the present study, and all were treated with mild hypothermia using the Thermogard XP (Alsius, USA) endovascular system. A target core temperature of 33 °C was maintained for 24 hours, with a subsequent rewarming rate of 0.15 °C per hour, followed by normothermia at 36.8 °C. Blood samples for the measurement of nitrotyrosine and nitrate/nitrite levels were drawn at admission and every 6 hours thereafter for two days. During the hypothermic period, the levels of nitrotyrosine and nitrates/nitrites were comparable with baseline values. During the rewarming period, serum levels of both parameters gradually increased and, during the normothermic period, the levels were significantly higher compared with hypothermic levels (nitrotyrosine, P<0.001; nitrates/nitrites, P<0.05). In our study, significantly lower levels of nitrotyrosine and nitrates/nitrites were demonstrated during hypothermia compared with levels during the normothermic period in adult CAS. These data suggest that attenuation of OS and NO production may be involved in the protective effect of hypothermia in adult CAS., A. Krüger ... [et al.]., and Obsahuje seznam literatury