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

Science with a small two-band UV-photometry mission III: Active Galactic Nuclei and nuclear transients

In this review (the third in the series focused on a small two-band UV-photometry mission), we assess possibilities for a small UV two-band photometry mission in studying accreting supermassive black holes (SMBHs; mass range $\sim 10^6$-$10^{10}\,M_{\odot}$). We focus on the following observational concepts: (i) dedicated monitoring of selected type-I Active Galactic Nuclei (AGN) in order to measure the time delay between the far-UV, the near-UV, and other wavebands (X-ray and optical), (ii) nuclear transients including (partial) tidal disruption events and repetitive nuclear transients, and (iii) the study of peculiar sources, such as changing-look AGN, hollows and gaps in accretion disks, low-luminosity AGN, and candidates for Intermediate-Mass Black Holes (IMBHs; mass range $\sim 10^2$-$10^5\,M_{\odot}$) in galactic nuclei. For tidal disruption events (TDEs), high-cadence UV monitoring is crucial for distinguishing among different scenarios for the origin of the UV emission. The small two-band UV space telescope will also provide the information about the near- and far-UV continuum variability for rare transients, such as repetitive partial TDEs and jetted TDEs. We also discuss the possibilities to study and analyze sources with non-standard accretion flows, such as AGN with gappy disks, low-luminosity active galactic nuclei with intermittent accretion, and SMBH binaries potentially involving intermediate-mass black holes.Comment: Submitted to Space Science Review

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

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

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

Effect of milking vacuum level and overmilking on cows’ teat characteristics

The influence of milking vacuum and milk flow level (resp. detachment level) on cows’ teat characteristics were studied in four experiments. The MIXED procedure was used to test treatment effects on the level of teat length, teat thickness at the base and half-way between the teat end and the base of udder, teat canal length, teat end width, teat wall thickness, teat cistern width after milking and on differences between these teat characteristics measured before and after milking. A total of 51 cows were included in all experiments. All the cows had clinically healthy udders. Some cows were involved in two or more experiments. Finally, 330 teat measurements of 165 cows were taken and statistically processed. Vacuum and milking with or without overmilking significantly (P < 0.05-0.001) influence monitored parameters. Milking vacuum has an influence on two of three measured external teat parameters: teat diameter measured at the base of the teat and half-way between the udder base and the teat tip. Change in teat length measured before and immediately after milking was higher when higher vacuum of 45 kPa was used. Detachment level also has an influence on teat proportions. Overmilked teats were longer and narrower compared to non-overmilked teats. Interaction between milking vacuum and detachment level influences external teat parameters as well