Oxidative stress induced by the Fe2+/ascorbic acid system or model ischemia in vitro: effect of carvedilol and pyridoindole antioxidant SMe1EC2 in young and adult rat brain tissue

New effective strategies and new highly effective neuroprotective agents are being searched for the therapy of human stroke and cerebral ischemia. The compound SMe1EC2 is a new derivative of stobadine, with enhanced antioxidant properties compared to the maternal drug. Carvedilol, a non-selective beta-blocker, possesses besides its cardioprotective and vasculoprotective properties also an antioxidant effect. We compared the effect of carvedilol and SMe1EC2, antioxidants with a similar chemical structure, in two experimental models of oxidative stress in young and adult rat brain tissue. SMe1EC2 was found to improve the resistance of hippocampal neurons to ischemia in vitro in young and even in 18-month-old rats and inhibited formation of protein carbonyl groups induced by the Fe2+/ascorbic acid pro-oxidative system in brain cortex homogenates of young rats. Carvedilol exerted a protective effect only in the hippocampus of 2-month-old rats and that at the concentration 10-times higher than did SMe1EC2. The inhibitory effect of carvedilol on protein carbonyl formation induced by the pro-oxidative system was not proved in the cortex of either young or adult rats. An increased baseline level of the content of protein carbonyl groups in the adult versus young rat brain cortex confirmed age-related changes in neuronal tissue and may be due to increased production of reactive oxygen species and low antioxidant defense mechanisms in the adult rat brain. The results revealed the new pyridoindole SMe1EC2 to be more effective than carvedilol in neuroprotection of rat brain tissue in both experimental models involving oxidative stress

Segmentation and supervised classification of image objects in Epo doping-control

Abstract A software system Gel Analysis System for Epo (GASepo) has been developed within an international WADA project. As recent WADA criteria of rEpo positivity are based on identification of each relevant object (band) in Epo images, development of suitable methods of image segmentation and object classification were needed for the GASepo system. In the paper we address two particular problems: segmentation of disrupted bands and classification of the segmented objects into three or two classes. A novel band projection operator is based on convenient object merging measures and their discrimination analysis using specifically generated training set of segmented objects. A weighted ranks classification method is proposed, which is new in the field of image classification. It is based on ranks of the values of a specific criterial function. The weighted ranks classifiers proposed in our paper have been evaluated on real samples of segmented objects of Epo images and compared t

Body distribution of 11C-methionine and 18FDG in rat measured by microPET

Compounds 18F-fluorodeoxyglucose (18FDG) and 11C-methionine (11C-MET) are radiodiagnostics frequently used in clinical Positron Emission Tomography (PET) as well in preclinical studies of various pathologies. The present study was focused on the comparison of biodistribution of both radiotracers in intact Wistar rats. The animals were scanned by microPET twice. The first scanning was done after 11C-MET administration, the second scan followed 5–7 days later using 18FDG. The radiotracers were injected into the tail vein of animals in isoflurane anesthesia. After a redistribution period, whole body scans were obtained using eXplore Vista SrT GE tomograph. Accumulation of the drugs in tissues was expressed in relative values (% ID/g) in selected regions of interest. As arbitrary reference tissue for drug accumulation, the sternoclavicular area was used. 18C-MET was found remarkably cumulating especially in the liver, spleen and distal part of the gastrointestinal tract. The compound was accumulated in the liver 6.9±0.92 (mean±SEM) times more intensively than in the reference tissue. The respective value for spleen and cecum/colon was 5.62±0.81 and 3.56±0.14 times. Accumulation of 11C-MET in other body parts including the brain and heart was very low and was apparently equal to the arbitrary tissue (0.13±0.01% ID/g). In the same animals 18FDG (biontFDG) was remarkably cumulated especially in Harderian glands compared to arbitrary tissue background (11.02±1.00 times), heart (7.52±1.70 times), brain (6.14±0.37 times), and colon (5.68±0.31 times). 18FDG accumulation in the liver, spleen and other organs was apparently not different from that found in the background (0.14±0.02% ID/g). The data obtained may serve as reference values in further microPET preclinical studies with 11C-MET and 18FDG under the given conditions

Anxiolytic activity of pyridoindole derivatives SMe1EC2 and SMe1M2: behavioral analysis using rat model

Anxiety and mood disorders have become very significant affections in the last decades. According to WHO at least one mental disease occurred per year in 27% of EU inhabitants (more than 82 mil. people). It is estimated that by 2020, depression will be the main cause of morbidity in the developed countries. These circumstances call for research for new prospective drugs with anxiolytic and antidepressive properties exhibiting no toxicity and withdrawal effect and possessing beneficial properties, like antioxidant and/or neuroprotective effects. The aim of this study was to obtain information about psychopharmacological properties of pyridoindole derivatives SMe1EC2 and SMe1M2, using non-invasive behavioral methods in rats

Protection of the vascular endothelium in experimental situations

One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo

Comparison of Novel Methods for Correlation Dimension Estimation

Abstract. We introduced and implemented two numerical method

Fractal complexity of EEG signal

Abstract. The paper deals with the presence of exponential or power-law decay in the power spectra of electroencephalogram (EEG). About 2300 EEG time series recorded during relaxed wakefulness were analysed. The whole spectrum of EEG was studied and power-law decay of about 2.28 prevailing over the exponential falling off was established. Correspondence between spectrum power-law decay and correlation dimension estimated for EEG was also validated

A novel minicollagen gene links cnidarians and myxozoans

Myxozoans are enigmatic endoparasitic organisms sharing morphological features with bilateria, protists and cnidarians. This, coupled with their highly divergent gene sequences, has greatly obscured their phylogenetic affinities. Here we report the sequencing and characterization of a minicollagen homologue (designated Tb-Ncol-1) in the myxozoan Tetracapsuloides bryosalmonae. Minicollagens are phylum-specific genes encoding cnidarian nematocyst proteins. Sequence analysis revealed a cysteine-rich domain (CRD) architecture and genomic organization similar to group 1 minicollagens. Homology modelling predicted similar three-dimensional structures to Hydra CRDs despite deviations from the canonical pattern of group 1 minicollagens. The discovery of this minicollagen gene strongly supports myxozoans as cnidarians that have radiated as endoparasites of freshwater, marine and terrestrial hosts. It also reveals novel protein sequence variation of relevance to understanding the evolution of nematocyst complexity, and indicates a molecular/morphological link between myxozoan polar capsules and cnidarian nematocysts. Our study is the first to illustrate the power of using genes related to a taxon-specific novelty for phylogenetic inference within the Metazoa, and it exemplifies how the evolutionary relationships of other metazoans characterized by extreme sequence divergence could be similarly resolved