Evaluation of neuroprotective activity of digoxin and semisynthetic derivatives against partial chemical ischemia

Recently, cardiotonic steroids (CTS) have been shown to lead to the activation of Na,K-ATPase at low concentrations in brain, promoting neuroprotection against ischemia. We report here the results of the use of digoxin and its semisynthetic derivatives BD-14, BD-15, and BD-16 against partial chemical ischemic induction followed by reperfusion in murine neuroblastoma cells neuro-2a (N2a). For chemical ischemic induction, sodium azide (5 mM) was used for 5 hours, and then reperfusion was induced for 24 hours. Na,K-ATPase activity and protein levels were analyzed in membrane preparation of N2a cells pretreated with the compounds (150 nM), in the controls and in induced chemical ischemia. In the Na,K-ATPase activity and protein levels assays, the steroids digoxin and BD-15 demonstrated a capacity to modulate the activity of the enzyme directly, increasing its levels of expression and activity. Oxidative parameters, such as superoxide dismutase (SOD) activity, lipid peroxidation (thiobarbituric acid reactive substance), glutathione peroxidase (GPx), glutathione (GSH) levels, hydrogen peroxide content, and the amount of free radicals (reactive oxygen species) during induced chemical ischemia were also evaluated. Regarding the redox state, lipid peroxidation, hydrogen peroxide content, and GPx activity, we have observed an increase in the chemical ischemic group, and a reduction in the groups treated with CTS. SOD activity increased in all treated groups when compared to control and GSH levels decreased when treated with sodium azide and did not change with CTS treatments. Regarding the lipid profile, we saw a decrease in the content of phospholipids and cholesterol in the chemical ischemic group, and an increase in the groups treated with CTS. In conclusion, the compounds used in this study demonstrate promising results, since they appear to promote neuroprotection in cells exposed to chemical ischemia.     

The omnivorous triggerfish Melichthys niger is a functional herbivore on an isolated Atlantic oceanic island

This study evaluated the functional role of the highly generalist omnivore Melichthys niger in the remote St. Peter and St Paul's Archipelago (SPSPA), Brazil, where grazing herbivorous fishes are very scarce. We analysed patterns of distribution from zero to 30 m deep during three time intervals during the day and sampled different aspects of their feeding behaviour, including diel feeding rate, feeding substrate and diet. The density of M. niger increased with depth (26–30 m) and decreased by the end of the day. Although M. niger did not present a typical herbivore diel feeding pattern, they targeted the epilithic algal matrix as their primary feeding substrate, ingesting predominantly algae and detritus. The characteristic Caulerpa racemosa var. peltata from SPSPA was ingested only as detached fronds. We suggest that in the isolated SPSPA, the single species M. niger may perform a unique role as a link between benthic primary production and higher levels. Further studies on the trophic ecology of omnivorous species are necessary to better understand their roles in a reef system, especially in impoverished areas where they are likely to play a crucial role.     

Dictyostelids from Mediterranean forests of the south of Europe

The first results of a study of dictyostelid diversity in soils of Mediterranean vegetation are presented. Surface soil samples were collected during 2003–2004 from different Mediterranean forests in Spain and Portugal and were plated out for cellular slime moulds. Isolated during this study were 14 species of dictyostelids. One species, Dictyostelium firmibasis is reported for the first time from Europe, and nine (Dictyostelium aureo-stipes, Dictyostelium sp. 1, Dictyostelium fasciculatum, Dictyostelium giganteum, Dictyostelium implicatum, Dictyostelium leptosomum, Dictyostelium sphaerocephalum, Polysphondylium candidum, Polysphondylium pallidum) are new records for the Mediterranean region. Members of the three genera Dictyostelium (ten species), Polysphondylium (three species) and Acytostelium (one species) are present in this region of the world. Comments on their diversity and distribution are included.     

Intrastriatal infusion of liver growth factor stimulates dopamine terminal sprouting and partially restores motor function in 6-hydroxydopamine-lesioned rats.

Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and may be useful for neuroregenerative therapies. The aim of this work was to investigate the effects of the intrastriatal (IS) infusion of LGF in the 6-hydroxydopamine rat model of Parkinson's disease. Tyrosine hydroxylase-positive innervation was significantly increased in the dopamine-denervated striatum of rats receiving intrastriatal LGF infusions (160 ng/day/rat x 15 days) as compared with a vehicle-infused group. There was no evidence of dopaminergic neurogenesis in the striatum or substantia nigra in any experimental group at the times studied. However, in those animals undergoing IS-LGF infusion for 48 hr, we found a significant increase in both microglial proliferation and in the number of microglial cells that acquired the ameboid morphology. This is characteristic of activated microglia/macrophages that has been reported to play an important role in dopamine terminal sprouting. In summary, our study shows that IS infusion of LGF stimulates the outgrowth of tyrosine hydroxylase-positive terminals in the striatum of 6-hydroxydopamine-treated rats. As apomorphine-induced rotational behavior was also reduced in these animals, we propose LGF as a novel factor that, when delivered to the striatum, may be useful in the treatment of Parkinson's disease.     

Circadian Variation with a Diurnal Bimodal Profile on Scent-Marking Behavior in Captive Common Marmosets (Callitrhix jacchus)

Scent-marking behavior is associated with different behavioral contexts in callitrichids, including signalizing a territory, location of feeding resources, and social rank. In marmosets and tamarins it is also associated with intersexual communication. Though it appears very important for the daily routine of the individuals, very few researchers have investigated distribution through the 24-h cycle. In a preliminary report, we described a preferential incidence of this behavior 2 h before nocturnal rest in families of common marmosets. We expand the data using 8 family groups (28 subjects), 8 fathers, 6 mothers, 8 nonreproductive adults (4 sons and 4 daughters), and 6 juvenile (3 sons and 3 daughters) offspring that we kept in outdoor cages under natural environmental conditions. We recorded the frequency of anogenital scent marking for each group during the light phase, twice a wk, for 4 consecutive wks, from March 1998 to September 1999. Cosinor test detected 24- and 8-h variations in 89.3% and 85.7% of the subjects, respectively, regardless of sex or reproductive status. The 8-h component is a consequence of the 2 peaks for the behavior, at the beginning and end of the light phase. Daily distribution of scent marking is similar to that others described previously for motor activity in marmosets. The coincident rhythmical patterns for both behaviors seem to be associated with feeding behavior, as described for callitrichids in free-ranging conditions, involving an increase in foraging activities early in the morning and shortly before nocturnal rest.