Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy.

It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.

Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system.

Ursolic acid, a constituent from Rosmarinus officinalis, is a triterpenoid compound which has been extensively known for its anticancer and antioxidant properties. In the present study, we investigated the antidepressant-like effect of ursolic acid isolated from this plant in two predictive tests of antidepressant property, the tail suspension test (TST) and the forced swimming test (FST) in mice. Furthermore, the involvement of dopaminergic system in its antidepressant-like effect was investigated in the TST. Ursolic acid reduced the immobility time in the TST (0.01 and 0.1mg/kg, p.o.) and in the FST (10mg/kg, p.o.), similar to fluoxetine (10mg/kg, p.o.), imipramine (1mg/kg, p.o.) and bupropion (10mg/kg, p.o.). The effect of ursolic acid (0.1mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with SCH23390 (0.05mg/kg, s.c., a dopamine D(1) receptor antagonist) and sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist). The administration of a sub-effective dose of ursolic acid (0.001mg/kg, p.o.) in combination with sub-effective doses of SKF38393 (0.1mg/kg, s.c., a dopamine D(1) receptor agonist), apomorphine (0.5µg/kg, i.p., a preferential dopamine D(2) receptor agonist) or bupropion (1mg/kg, i.p., a dual dopamine/noradrenaline reuptake inhibitor) reduced the immobility time in the TST as compared with either drug alone. Ursolic acid and dopaminergic agents alone or in combination did not cause significant alterations in the locomotor and exploratory activities. These results indicate that the antidepressant-like effect of ursolic acid in the TST is likely mediated by an interaction with the dopaminergic system, through the activation of dopamine D(1) and D(2) receptors.

α-smooth muscle actin, fibrillin-1, apoptosis and proliferation detection in primary varicose lower limb veins of women.

AIM: The role of SMC apoptosis and proliferation was correlated to the amount of fibrillin and alfa-smooth muscle actin of primary varicose veins. METHODS: Twenty varicose vein specimens were atraumatically harvested from 20 women undergoing lower extremity primary varicose vein excision. The patients were divided into groups according to age (<50 years, >50 years) and the presence of leg edema (CEAP, class 2 or 3). The surface density of fibrillin-1 fibers (Sv([Fbn-1])), the volume density of smooth muscle cells: (Vv([SMC])), the number of proliferating and apoptotic cells per area. Quantitative data comparisons between class and age groups were performed. RESULTS: The median value of Vv([SMC]) was 16% greater and the Sv([Fbn-1]) was 35% greater in the intima vein sections from patients up to 50y compared to >50y. Apoptosis was found more frequent in veins sections from varicose women >50y. In the media layer, Sv([Fbn-1]) in veins from patients up to 50y was more important, and women with >50y had also more cells in apoptosis. Vv([SMC]) from women without edema (CEAP-Class 2) was 28% greater in the intima and apoptotic cells were more prominent in the intima of women with edema (CEAP-Class 2). In the media layer, Sv([Fbn-1]) was 12,5% greater in veins from women without edema and apoptosis was more detected in the veins from patients with edema. CONCLUSION: Age of the patient may affect the remodeling of varicose veins and SMC quantity in the media layer was found decreased in patients with edema.

Chemical composition and microbicidal activity of extracts from Brazilian and Bulgarian propolis.

AIMS: The chemical composition of ethanol extracts from a Brazilian (Et-Bra) and a Bulgarian (Et-Blg) propolis, and their activity against the protozoan Trypanosoma cruzi, several fungi and bacteria species were determined. METHODS AND RESULTS: The chemical composition was determined by high temperature high resolution gas chromatography coupled to mass spectrometry. Microbiological activity was assayed in vitro against T. cruzi, Candida albicans, Sporothrix schenckii, Paracoccidioides brasiliensis, Neisseria meningitidis, Streptococcus pneumoniae and Staphylococcus aureus. CONCLUSIONS: Et-Bra and Et-Blg, although with totally distinct compositions, were active against T. cruzi and the three species of fungi. Et-Blg was more effective than Et-Bra against bacteria, particularly N. meningitidis and Strep. pneumoniae. SIGNIFICANCE AND IMPACT OF THE STUDY: Although with different classes of components, both propolis extracts showed microbicidal activity. For the bactericidal activity it was possible to establish a positive correlation with the high content of flavonoids of the Bulgarian extract.

Projection of the marginal shell of the anteroventral cochlear nucleus to olivocochlear neurons in the cat.

The marginal shell of the anteroventral cochlear nucleus is anatomically and physiologically different from its central core. Previous studies suggest that neurons in the marginal shell are well suited to encode the intensity of acoustic stimuli. To investigate the projections of the marginal shell, a focal injection (<100 nl) of a mixture of biotinylated dextran amine (BDA) and (3)H-leucine was made into the marginal shell of the cat combined with injection of cholera toxin subunit-B (CTB) into the cochleas. Following a 7-day survival, the cats were perfused. Axons and swellings labeled with BDA and olivocochlear neurons labeled with CTB were immunocytochemically stained black and brown, respectively. (3)H-leucine labels were visualized by autoradiography. Labeled neural structures were examined via light microscopy. We found that swellings labeled with BDA, sometimes doubly labeled with BDA and (3)H-leucine, were in close apposition with dendrites and/or somata of olivocochlear neurons identified with CTB labeling. Double labeling with BDA and (3)H-leucine signifies that the label was anterogradely transported. The results support the conclusion that the anteroventral cochlear nucleus projects to medial olivocochlear neurons bilaterally and to lateral olivocochlear neurons ipsilaterally. Furthermore, the results are consistent with the interpretation that the marginal shell provides a source of the above-mentioned projections. Together with information in the literature, the present anatomical results support a hypothesis that the marginal shell provides information about stimulus intensity as a part of a reflex (or feedback gain control) system comprising the cochlea, cochlear neurons, cochlear nucleus, medial olivocochlear neurons, and cochlear outer hair cells.