Mental stress in psychiatric disease and in daily life contributes to oxidative stress in the body. In this study we investigated a connection between possible psychological stress caused by university undergraduate examinations and oxidative stress experienced by our test subjects. Some parameters of oxidative stress (single strand breaks of DNA in lymphocytes, sensitivity to lipid oxidation and antioxidant status) were studied in medical students on the day of the examination (stress condition) and compared with the same parameters obtained from the same students during the term between two examination periods (non-stress condition). The results show that in the stress condition oxidative damage to DNA and sensitivity to lipid oxidation were significantly increased (p<0.05) when compared with the same parameters in "non-stress" conditions. A significant decrease in plasma antioxidant activity (p<0.05) in students that were under stress was observed. These results suggest that during university examinations students are under increased oxidative stress.

The purpose of this randomized, double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol (Pyc) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on the total antioxidant status (TAS) in children with attention deficit/hyperactivity disorder (ADHD).We have found significantly increased damage to DNA in ADHD children when compared to controls. 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group. TAS in ADHD children was lower in comparison to controls. After Pyc administration, TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application. Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children. In conclusion, Pycnogenol(R) administration reduces oxidative damage to DNA, normalizes TAS and improves attention of ADHD children. Explanation of mutual relation between oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pyc's action needs further investigations.

Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics. The recent studies suggest that the interaction between Hcy and mitochondria is complex, and reactive oxygen species (ROS) are possible mediators of Hcy effects. We focus on mechanisms contributing to HHcy-associated oxidative stress, such as sources of ROS generation and alterations in antioxidant defense resulting from altered gene expression and post-translational modifications of proteins. Moreover, we discuss some recent findings suggesting that HHcy may have beneficial effects on mitochondrial ROS homeostasis and antioxidant defense. A better understanding of complex mechanisms through which Hcy affects mitochondrial functions could contribute to the development of more specific therapeutic strategies targeted at HHcy-associated disorders.

Simvastatin is a cholesterol-lowering agent whose functional significance and neuroprotective mechanism in ischemic brain injury is not yet solved. The purpose of this study is to evaluate the effect of simvastatin on ischemic brain injury. We examined the endoplasmic reticulum stress response (UPR/unfolded protein response), by measuring the mRNA and protein levels of specific genes such as ATF6, GRP78, and XBP1 after 15 min 4-VO ischemia and different times of reperfusion (1, 3, and 24 h). The results from the group of naïve ischemic rats were compared with results from the group of pre-treated animals with simvastatin. The results of the experiments showed significant increase in all genes at the mRNA level in ischemic phase (about 43% for XBP1, 58% for GRP78, and 39% for ATF6 more than control). The protein level of XBP1 was decreased in pre-treated animals at ischemic phase and first hour of reperfusion (about 15% less), and did not reach control levels. The protein levels of GRP78 were maximal at third hour of reperfusion in statin group with a small decrease at 24 h of reperfusion in both groups. The levels of ATF6 mRNA in statin-treated animals was higher in comparison to non-statin animals at the ischemic phase and the third hour of reperfusion (about 35% higher), which was also translated into the higher protein level. This could indicate that one of the main proteins targeted to enhance neuroprotective effect to ER during the first two hours of reperfusion was ATF6 protein, the levels of which were 60% higher than in non-treated animals. These data suggest that simvastatin, in addition to the proposed neuroprotective effect, exerts a neuroprotective role in the attenuation of ER stress response after acute ischemic/reperfusion insult.

One month of Pycnogenol administration (1 mg/kg body weight/day) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a placebo. TAS in children with ADHD was decreased in comparison with reference values. Pycnogenol administration normalizes TAS of ADHD children.

Ischemic preconditioning (IPC) represents the phenomenon of CNC adaptation, which results in increased tolerance of CNS to lethal ischemia. Brain ischemia/reperfusion (IRI) initiates a catastrophic cascade in which many subcellular organelles play an important role. The Golgi apparatus, which is a part of secretory pathways (SP), represents the Ca(2+) store and regulates secretion of proteins for growth/reorganization of neuronal circuit by secretory Ca(2+)ATPases (SPCA1). The purpose of this study is to evaluate the effect of IRI and preconditioning on SPCA1 gene expression and oxidative damage after 4-vessel occlusion for 15 min and after being exposed to different reperfusion periods. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later, 15 min of lethal ischemia was induced. Our experiments conclusively showed IRI-induced depression of SPCA activity and lipo- and protein oxidation in rat hippocampal membranes. IRI also activates the induction of SPCA1 gene expression in later reperfusion periods. IPC partially suppresses lipo- and protein oxidation in hippocampal membranes and leads to partiall rovery of the ischemic-induced depression of SPCA activity. In addition, IPC initiates earlier cellular response to the injury by the significant elevation of mRNA expression to 142% comparing to 1 h of corresponding reperfusion and to 11% comparing to 24 h of corresponding reperfusion, respectively. Similar patterns were observed on the translational level by Western blot analysis. Our results indicate the specific SPCA1 expression pattern in ischemic hippocampus. It also shows that the SPCA expression and the post-translational changes induced by ischemia are modulated by the IPC. This might serve to understand the molecular mechanisms involved in the structural integrity and function of the SP after ischemic challenge. It also suggests that there is a correlation of SPCA function with the role of SP in the response to pre-ischemic challenge.

BackgroundIt has been suggested that polymorphisms in glutathione-S-transferases (GST) could predispose to prostate cancer through a heritable deficiency in detoxification pathways for environmental carcinogens. Yet, studies linking GST polymorphism and prostate cancer have so far failed to unambiguously establish this relation in patients. A retrospective study on healthy, unrelated subjects was conducted in order to estimate the population GST genotype frequencies in the Slovak population of men and compare our results with already published data (GSEC project-Genetic Susceptibility to Environmental Carcinogens). A further aim of the study was to evaluate polymorphisms in GST also in patients with prostate cancer in order to compare the evaluated proportions with those found in the control subjects.MethodsWe determined the GST genotypes in 228 healthy, unrelated subjects who attended regular prostate cancer screening between May 2005 and June 2007 and in 129 histologically verified prostate cancer patients. Analysis for the GST gene polymorphisms was performed by PCR and PCR-RFLP.ResultsWe found that the GST frequencies are not significantly different from those estimated in a European multicentre study or from the results published by another group in Slovakia. Our results suggest that Val/Val genotype of GSTP1 gene could modulate the risk of prostate cancer, even if this association did not reach statistical significance. We did not observe significantly different crude rates of the GSTM1 and GSTT1 null genotypes in the men diagnosed with prostate cancer and those in the control group.ConclusionUnderstanding the contribution of GST gene polymorphisms and their interactions with other relevant factors may improve screening diagnostic assays for prostate cancer. We therefore discuss issues of study feasibility, study design, and statistical power, which should be taken into account in planning further trials.

Androgens and androgen receptor (AR) play a critical role not only in normal prostate development, but also in prostate cancer. For that reason, androgen deprivation therapy (ADT) is the primary treatment for prostate cancer. However, the majority of patients develop castration-resistant prostate cancer, which eventually leads to mortality. Novel therapeutic approaches, including dietary changes, have been explored. Soy isoflavones have become a focus of interest because of their positive health benefits on numerous diseases, particularly hormone-related cancers, including prostate and breast cancers. An important strategy for the prevention and/or treatment of prostate cancer might thus be the action of soy isoflavones on the AR signaling pathway. The current review article provides a detailed overview of the anticancer potential of soy isoflavones (genistein, daidzein and glycitein), as mediated by their effect on AR. Contents 1. Introduction 2. AR: Structure, function and mechanism of action 3. Isoflavones: Structures, sources and general biological activities 4. Hormone-like properties of isoflavones 5. Isoflavones as AR modulators: Interactions with AR 6. Isoflavones as AR modulators: In vitro and in vivo studies and clinical trials on prostate cancer 7. Isoflavones and metabolism of steroid hormones 8. Conclusions