Plasma lipoprotein(a) concentration as an independent predictor of hemodynamic progression of aortic valve stenosis.

Calcific aortic valve disease (CAVD) is a common cardiovascular disorder of high social significance. This study aimed to identify independent predictors of hemodynamic progression of CAVD. The relationship between some risk factors, including the rs10455872 polymorphism in the intron 25 of the lipoprotein(a) [Lp(a)] coding region and the plasma Lp(a) concentration, and CAVD severity were prospectively examined in 114 patients. Age (p = 0.023), smoking (p = 0.038), lack of obesity (p = 0.005), triglyceride levels (p = 0.039), and plasma Lp(a) (p < 0.0001) levels were found to be significant determinants of stenosis progression. The rs10455872 polymorphism; however, was not found to be a significant factor for neither the stenosis severity (p = 0.773) nor for plasma Lp(a) levels (p = 0.617). We established a highly significant Lp(a) cut-off concentration (21.2 mg/dL) distinguishing the aortic valve calcification without stenosis from the significant stenosis. Plasma Lp(a) concentration was the only independent predictor of disease progression (p < 0.0001). Moreover, patients with plasma levels of Lp(a) ≥ 21.2 mg/dL were 55 times more likely to develop aortic valve stenosis. We conclude that Lp(a) concentration may prove valuable for more reliable identification of patients at risk of accelerated CAVD development. Future studies are desirable to determine whether plasma Lp(a) levels could be used as a potential biomarker for aortic stenosis progression.

Cognitive impairment one year after ischemic stroke: predictorsand dynamics of significant determinants.

BACKGROUND/AIM: Evidence suggests that the risk for dementia increases after stroke. This study investigated the dynamics of the neurological and cognitive status of patients with no baseline dementia over a 1-year period after ischemic stroke. MATERIALS AND METHODS: We examined 47 ischemic stroke patients admitted within 48 h of ictus. Their neurological and cognitive statuses, blood biochemical parameters, and microalbuminuria levels were prospectively evaluated over a 1-year period post-stroke. RESULTS: A more severe neurological deficit was found in the cognitively impaired patients (P = 0.003). The NIHSS score over a 1-year follow-up period improved only in patients with normal cognition (P = 0.000). Time-varying dynamics of the MMSE score were observed in both patient groups (P = 0.000). Age (Р = 0.000), education (Р = 0.004), sex (Р = 0.041), history of diabetes (Р = 0.045), and serum high sensitive C-reactive protein (hs-CRP) on admission (Р = 0.003) were significant determinants of cognitive decline 1 year after a stroke. The albumin-to-creatinine ratio was high during the whole follow-up period in the cognitively impaired group after adjusting for sex and age (P = 0.010). Binary logistic regression showed that hs-CRP (Р = 0.013) and age (Р = 0.010) were independent predictors of patients' cognitive status 1 year after stroke. CONCLUSION: The level of inflammatory markers could be considered as an additional criterion of long-term cognitive impairment.

Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats.

Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR.

Serum C-reactive protein and lipid hydroperoxides in predicting short-term clinical outcome after spontaneous intracerebral hemorrhage.

There is no effective treatment for spontaneous intracerebral hemorrhage (sICH). We examined 46 patients with sICH within 48 hours after onset of symptoms, aiming to assess the predictive value of C-reactive protein (CRP) and lipid hydroperoxides (ROOH) on "first-week mortality" and "clinical outcome at discharge" by binary logistic regression. We found that serum CRP and hematoma volume were predictors of short-term mortality. Although serum ROOH level was positively correlated with mortality, it did not predict early lethal outcome. Serum ROOH concentration, however, was a predictor of poor clinical outcome in sICH survivors. After confirmation of the results obtained through observing a larger group of patients, an oxidative stress marker could be used as an additional criterion for patient stratification, especially when severe disability is expected and supplementary therapeutic approaches are urgent.

Reduced extracellular phagocyte oxidative activity, antioxidant level changes and increased oxidative damage in healthy human blood as a function of age.

Age-related changes in the blood antioxidant status, in the prooxidative activity of peripheral phagocytes and in the markers of oxidative injury were simultaneously examined in the circulation of 45 middle-aged and elderly healthy volunteers. The results showed a decrease in the opsonin-dependent and -independent extracellular-phagocyte oxidative activity, evaluated by means of luminol chemiluminescence. An increase in the portion of the mitochondrial superoxide generation within the total oxidative phagocyte response was evaluated by means of lucigenin chemiluminescence. The erythrocyte copper/zinc superoxide dismutase increased with age, while blood catalase and glutathione peroxidase activities remained unchanged. The levels of blood SH-groups decreased with age. An age-related increase in blood concentration of thiobarbituric acid-reactive material, a marker of oxidative damage, was detected. Some data, illustrating the existence of a delicate balance between oxidants and prooxidants, were also obtained. Further studies on the interrelationship between the components determining pro/antioxidative status in an organism may prove useful for developing a complex strategy in combating ageing.

What happens with ageing: decline or remodeling of opsonin-independent phagocyte oxidative activity?

Changes that occur with age in the opsonin-independent oxidative activity of peripheral phagocytes in whole blood were examined by means of luminol chemiluminescence (LCL). The chemiluminescence was registered simultaneously by non-stimulated and stimulated cells and the age-related alterations of total and extracellular generation of reactive oxygen species (ROS) were studied using model systems. It was found that the rate of phagocyte activation by the glass surface of the measuring chambers, assessed by the time of the peak appearance after the start of LCL response, increased. However, the maximum oxidative activity and the integral oxidative capacity of the cells during adhesion, evaluated by the maximum LCL intensity and the area under the LCL curve, respectively, declined. No age-dependence of formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated oxidative cellular activity for total ROS generation was detected. The maximum oxidative activity and the integral oxidative capacity of peripheral phagocytes to generate extracellular superoxide in response to fMLP was decreased. The likely causes for the observed alterations in phagocyte function are discussed and an analysis of the obtained results is given on the background of the contradictory data published on phagocyte oxidative activity age-related changes.

Zinc content in the diet affects the activity of Cu/ZnSOD, lipid peroxidation and lipid profile of spontaneously hypertensive rats.

The present study focused on the effect of Zn containing diets on the activity of superoxide dismutase (Cu/ZnSOD), systolic blood pressure (SBP), lipid peroxides (ROOH) and lipids (LDL, HDL, triglycerides and cholesterol) in male spontaneously hypertensive rats (SHR). Three experimental groups of animals were studied: a control (G1-40 mg), and two with zinc-supplemented diets (G2-100 and G3-160 mg Zn/kg lab chow). The diets were introduced at the beginning of the development of hypertension (2 months after birth) and the animals were fed for 8 weeks. The activity of CuZnSOD in erythrocytes was determined by spectrophotometry with the use of RANSOD kit (RANDOX Laboratories Ltd., UK). Atomic-absorption spectrometry was used to determine Zn and Cu concentrations in the rat's sera. A significantly increased Cu/ZnSOD activity was found in G3 compared with rats fed with control diet G1 (p = 0.020). SBP was significantly decreased in G3 in relation to G1 (p = 0.0048). The lipid hydroperoxide concentration was significantly decreased in G3 compared with G1 (p = 0.016) and G2 (p = 0.005). Zinc supplement affected lipids profile by decreasing LDL and increasing HDL. The present data suggest that Zn concentration in the diet plays an important role in the regulation of SBP and can be a critical nutrient for maintenance of anti-oxidative events in SHR.

Inhibitory and enhancing effects of piroxicam on whole blood chemiluminescence.

The effects of piroxicam on the production of reactive oxygen species by stimulated phagocytes was studied in whole blood by a chemiluminescence (CL) technique in relation to maximum activity, localization and kinetics of radical generation. We found that piroxicam dose-dependently inhibited total (intra- and extracellular) zymosan-stimulated luminol CL (LCL) at a high stimulant concentration (p = 0.0001). Piroxicam additionally decreased cytochalasin B-reduced LCL, which shows that the effect of the drug should be sought in the extracellular component of the response. Piroxicam inhibited the first phase of extracellular LCL in a dose-dependent manner (p = 0.0001) and revealed itself as an enhancing agent of CL in later time intervals after the start of respiratory burst, in a model system containing horseradish peroxidase (HRP) and sodium azide. It enhanced LCL of a cell-free system, i.e. influenced the CL due to HRP-catalysed decomposition of hydrogen peroxide. It also dose-dependently inhibited the early extracellular superoxide production, evaluated by lucigenin CL (p = 0.022). Piroxicam inhibited the total fMLP-stimulated LCL by 70% approximately and, only by about 30%, the first phase of fMLP-stimulated extracellular LCL, which presupposes an effect on myeloperoxidase-catalysed formation of hypochloric acid. Piroxicam slightly increased the intracellular LCL by phagocytes (p = 0.02), an effect that is probably connected with its ability to induce the release of secondary messengers in signal transduction. In conclusion, the anti-inflammatory effect of piroxicam is probably related to the inhibition of the extracellular generation of superoxide and hypochloric acid in the early stages of phagocyte activation.

Oxidative stress during the chronic phase after stroke.

Stroke is a complex disease originating and developing on the background of genetic predisposition and interaction between different risk factors that chronically damage blood vessels. The search for an effective treatment of stroke patients is the main priority of basic and clinical sciences. The chronic phase of stroke provides possibilities for therapy directed toward stimulation of recovery processes as well as prophylaxis, which reduces the probability of subsequent cerebrovascular events. Oxidative stress is a potential contributor to the pathophysiological consequences of stroke. The aim of the present review is to summarize the current knowledge of the role of oxidative stress during the chronic phase after stroke and its contribution to the initiation of subsequent stroke. The relationship among inflammation, hemostatic abnormalities, and platelet activation in chronic stroke patients is discussed in the context of ongoing free radical processes and oxidative damage. Free radical-mediated effects of increased plasma level of homocysteine and its possible contribution to the processes leading to recurrent stroke are discussed as well. The status of the antioxidant defense system and the degree of oxidative damage in the circulation of stroke survivors are examined. The results are interpreted in view of the effects of the vascular risk factors for stroke that include additional activation of inflammatory and free radical mechanisms. Also, the possibilities for combined therapy including antioxidants in the acute and convalescent stages of stroke are considered. Future investigations are expected to elucidate the role of free radical processes in the chronic phase after stroke and to evaluate the prophylactic and therapeutic potential of anti-radical agents.

Dynamics of free radical processes in acute ischemic stroke: influence on neurological status and outcome.

The dynamics of free radical processes during the acute stage of ischemic stroke and their relationship with the clinical status of patients were studied. An enhanced extracellular generation of reactive oxygen species (ROS) by peripheral phagocytes was observed in severe stroke patients during the whole acute stage. This generation correlated positively with the size of infarct, the severity of neurological deficit and handicap and correlated negatively with the improvement of the neurological status of patients. An increase in the activity of two enzymes from the antioxidant defense mechanism, catalase and glutathione peroxidase, was registered during the whole acute phase of stroke, regardless of its severity. The concentration of lipid peroxidation products increased over time. Blood concentration of thiobarbituric acid-reactive material (TBARM) correlated positively with the size of infarct, the severity of neurological deficit and handicap. In conclusion, extracellular ROS generation by phagocytes and blood TBARM concentration could be used as indicators for stroke outcome.

Oxidative stress in the chronic phase after stroke.

The spontaneous and the stimulated extracellular generation of reactive oxygen species (ROS) by peripheral phagocytes, the blood antioxidant capacity and the degree of oxidative damage were evaluated in patients with severe ischemic and hemorrhagic stroke in the chronic phase of disease. It was found in patients compared to the control group that: (i) the spontaneous phagocyte oxidative activity was enhanced independently of the type of stroke and the time elapsed after stroke onset; (ii) there was no difference in the extracellular ROS generation stimulated by opsonin-dependent and independent receptor mechanisms; (iii) there was no change in the indices of blood antioxidant capacity; (iv) the concentration of plasma lipid peroxides was enhanced regardless of the type of stroke, but it significantly increased over time; and (v) the concentration of blood thiobarbituric acid-reactive material was also enhanced. It was independent of the type of stroke and remained elevated during the whole period studied. We have demonstrated an enhanced spontaneous phagocyte oxidative activity and oxidative damage to lipids in patients in the chronic phase after stroke. The elimination of generated ROS and products of lipid peroxidation from the circulation could prevent the aggravation of chronic vascular injury in patients and could reduce the possibility of a subsequent stroke. This suggests the need for complex therapy, including antioxidant treatment directed to exclude the effects of free radicals, after the oxidative stress of stroke.