Cytokine interplay among the diseased retina,inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy

Retinal degenerative disorders, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration or glaucoma, represent the most common causes of loss of vision and blindness. In spite of intensive research, treatment options to prevent, stop or cure these diseases are limited. Newer therapeutic approaches are offered by stem cell-based therapy. To date, various types of stem cells have been evaluated in a range of models. Among them, mesenchymal stem/stromal cells (MSCs) derived from bone marrow or adipose tissue and used as autologous cells have been proposed to have the potential to attenuate the negative manifestations of retinal diseases. MSCs delivered to the vicinity of the diseased retina can exert local anti-inflammatory and repair-promoting/regenerative effects on retinal cells. However, MSCs also produce numerous factors that could have negative impacts on retinal regeneration. The secretory activity of MSCs is strongly influenced by the cytokine environment. Therefore, the interactions among the molecules produced by the diseased retina, cytokines secreted by inflammatory cells and factors produced by MSCs will decide the development and propagation of retinal diseases. Here we discuss the interactions among cytokines and other factors in the environment of the diseased retina treated by MSCs, and we present results supporting immunoregulatory and trophic roles of molecules secreted in the vicinity of the retina during MSC-based therapy.     

Seasonal variability of oxidative stress markers in city bus drivers. Part II. Oxidative damage to lipids and proteins

The aim of the present study was to investigate the seasonal variability of markers of oxidative damage to lipids (15-F2t-isoprostane, 15-F2t-IsoP) and proteins (protein carbonyl levels) in 50 bus drivers and 50 controls from Prague, Czech Republic, and to identify factors affecting oxidative stress markers. The samples were collected in three seasons with different levels of air pollution. The exposure to environmental pollutants (carcinogenic polycyclic aromatic hydrocarbons, c-PAHs, particulate matter, PM2.5 and PM10, and volatile organic compounds, VOC) was monitored by personal and/or stationary monitors. For the analysis of both markers, ELISA techniques were used. The median levels of individual markers in bus drivers versus controls were as follows: 15-F2t-IsoP (nmol/mmol creatinine): winter 2005, 0.81 versus 0.68 (p<0.01); summer 2006, 0.62 versus 0.60 (p=0.90); winter 2006, 0.76 versus 0.51 (p<0.001); carbonyl levels (nmol/ml plasma): winter 2005, 14.1 versus 12.9 (p=0.001); summer 2006, 17.5 versus 16.6 (p=0.26); winter 2006, 13.5 versus 11.7 (p<0.001). Multivariate logistic regression identified PM levels measured by stationary monitors over a period 25-27 days before urine collection as a factor positively associated with lipid peroxidation, while protein oxidation levels correlated negatively with both c-PAHs and PM levels. In conclusion, markers of oxidative damage to lipids and proteins were increased in bus drivers in winter seasons, but not in summer. Lipid peroxidation was positively correlated with c-PAHs and PM exposure; protein oxidation correlated negatively and was highest in summer suggesting another factor(s) affecting protein carbonyl levels.     

Effect of L-carnitine against acute mitoxantrone toxicity in mice

Various experiments were performed in our laboratory to define a possible role for carnitine derivatives in mitoxantrone (MX) therapy. We report here the results of the effect of L-carnitine (LCAR) on the lethal toxicity of MX in mice. MX was administered intravenously at doses of 7, 9, 11, 13, 15 or 17 mg kg⁻¹ either alone or in combination with LCAR at a single intravenous dose of 200 mg kg⁻¹. The dependence of the probability of death on various doses was evaluated for the MX-LCAR combination compared to MX alone. From these experiments, the following lethal dose fifty (LD₅₀) values were calculated: LD₅₀ for MX alone was 15.2 mg kg⁻¹, whereas in combination with LCAR it increases to 21.8 mg kg⁻¹. The relative toxicity given as the ratio of the LD50 of both MX alone and the combination of MX-LCAR was 69.7%. The results of our experiments unequivocally show the effect of LCAR on acute toxic doses of MX.     

Isolated Asian steppe element in the Balkans: habitats of <Emphasis Type="Italic">Proterebia afra</Emphasis> (Lepidoptera: Nymphalidae: Satyrinae) and associated butterfly communities

A characteristic butterfly of Asian steppes, Proterebia afra (Fabricius 1787), was studied in its two relic areas of occurrence within the Balkans—the Askion Mts (a single mountain massif in NW Greece) and Dalmatia (karstic inland S Croatia)—together with co-occurring butterfly communities during its early spring adult flight period. P. afra adults tolerate harsh continental conditions prevailing at its localities during its flight. Local densities were higher in the Askion Mts (up to 100 individuals per 50 m walk) than in Dalmatia (up to 30 individuals per 50 m). Within both areas of occurrence, it inhabits dry grasslands subject to intermediate grazing pressure that retains enough dry grass litter but still suppresses shrubs and trees. Hotter slopes are preferred in more northerly Dalmatia than in the more southerly Askion Mts. More co-occurring butterfly species and more Mediterranean species were recorded in the Askion Mts (69 vs 63; 23 vs 12), but more butterfly individuals and higher species’ richness per transect were observed in Dalmatia. In ordination analyses, the main gradients organising the grassland butterfly communities distinguished between grassy plains and rocky slopes containing more woody plants. Given the distribution extents, local densities and present land use conditions, the Balkan P. afra is not currently endangered, but this may swiftly change with grazing abandonment, especially in Dalmatia, and some conservation actions should be considered in the near future.     

The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response

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