The Streptomyces metabolite anhydroexfoliamycin ameliorates hallmarks of Alzheimer's disease in vitro and in vivo.

Anhydroexfoliamycin (1) and undecylprodigiosin (2) have been previously described as neuroprotective molecules against oxidative stress in neurons. Since oxidative stress is strongly correlated with neurodegenerative diseases, we have evaluated their effects over the principal hallmarks of Alzheimer's disease (AD). Both compounds were tested in vitro in two different neuroblastoma cellular models, one for amyloid precursor protein metabolism studies (BE(2)-M17) and another one specific for taupathology in AD (SH-SY5Y-TMHT441). Amyloid-beta (Aß) levels, ß-secretase (BACE1) activity, tau phosphorylation, extracellular signal-regulated kinase (ERK) and glycogen synthase kinase-3beta (GSK3ß) expression were analyzed and while undecylprodigiosin (2) produced poor results, anhydroexfoliamycin (1) strongly inhibited GSK3ß, reducing tau phosphorylation in vitro (0.1 µM). A competitive assay of anhydroexfoliamycin (1) and the specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, showed that the reduction of the phosphorylated tau levels is mediated by the JNK pathway in SH-SY5Y-TMHT441 cells. Thus, this compound was tested in vivo by intraperitoneal administration in 3xTg-AD mice, confirming the positive results registered in the in vitro assays. This work presents anhydroexfoliamycin (1) as a promising candidate for further studies in drug development against neurodegenerative diseases.

Bromoalkaloids protect primary cortical neurons from induced oxidative stress.

Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases.

Behaviour of enzymatic activities and root elongation in Argiudoll soils from the Argentine Humid Pampa treated with biosolids.

The incorporation of biosolids to soil is a strategy aiming at the re-location of these materials in the environment with a useful end: soil fertilization. In this work, the response of two Argiudoll soils (one with more than 100 years of agriculture and the other, a virgin one) to biosolid incorporation was studied under laboratory conditions. To measure this response, soil enzymatic biodescriptors, such as dehydrogenase and urease activities, and tests related to plant physiology (the root elongation test) were employed. The addition of the biosolid to both soils had a stimulating effect though different on each soil according to the added dose. Adjustment of the regression line for dehydrogenase activity with root elongation was positive and statistically significant (p<0.001). Results suggest that biodescriptors employed were suitable for studying the impact of amended biosolids on different soils.

Evaluation of various tests for the diagnosis of soil contamination by 2,4,5-trichlorophenol (2,4,5-TCP).

Soil response to contamination with 2,4,5-triclorophenol was studied to test the validity of the concept of Generic Reference Levels (GRL), the main criterion used to define soil contamination. Soil samples were artificially contaminated with doses between 0 and 5000 mg kg(-1) of 2,4,5-triclorophenol, and analysed by various tests. Where possible, the response of soils to the contaminant was modelled by a sigmoidal dose-response curve in order to estimate the ED(50) values. The tests provided different responses, but only microbial biomass-C and dehydrogenase and urease activities demonstrated soil deterioration in response to contamination. The results suggest that the diagnosis of soil contamination has been greatly simplified in the legislation by the provision of a single figure for each compound, and that the GRL concept could perhaps be substituted by measurement of ED(50) values, which better reflect the alteration of a soil due to the presence of a xenobiotic substance.

Behaviour of enzymatic activities and root elongation in Argiudoll soils from the Argentine Humid Pampa treated with biosolids / Comportamiento de actividades enzimáticas y elongación de raíces en suelos Argiudoles de la Pampa Húmeda, Argentina, tratados con biosólidos

The incorporation of biosolids to soil is a strategy aiming at the re-location of these materials in the environment with a useful end: soil fertilization. In this work, the response of two Argiudoll soils (one with more than 100 years of agriculture and the other, a virgin one) to biosolid incorporation was studied under laboratory conditions. To measure this response, soil enzymatic biodescriptors, such as dehydrogenase and urease activities, and tests related to plant physiology (the root elongation test) were employed. The addition of the biosolid to both soils had a stimulating effect though different on each soil according to the added dose. Adjustment of the regression line for dehydrogenase activity with root elongation was positive and statistically significant (p<0.001). Results suggest that biodescriptors employed were suitable for studying the impact of amended biosolids on different soils.

La incorporación de biosólidos al suelo es una estrategia que tiene como objetivo la reubicación de estos materiales en el ambiente con un fin útil, como es la fertilización del suelo. En este trabajo se estudió, en condiciones controladas de laboratorio, la respuesta de dos suelos Argiudoles (uno con más de 100 años de agricultura y otro virgen) frente a la perturbación físico-química y biótica que genera la incorporación de un biosólido. Para medir esta respuesta se emplearon dos biodescriptores edáficos (las actividades deshidrogenasa y ureasa) y un tercero referido a la fisiología vegetal, la prueba de elongación de raíces. La incorporación del biosólido en ambos suelos, en general no deprimió el funcionamiento de las actividades enzimáticas estudiadas; contrariamente, según la dosis aportada tuvo un efecto estimulante, aunque diferente, entre ambos suelos. El ajuste de la recta de regresión de la actividad deshidrogenasa con la elongación de las plántulas fue positivo y altamente significativo, lo que indica la complementaridad de ambos descriptores. Los resultados obtenidos sugieren que los biodescriptores empleados resultaron aptos para estudiar el impacto que produce la incorporación de biosólidos a suelos agrícolas.

Biochemical properties of vineyard soils in Galicia, Spain.

In the present study we investigated changes in soil biochemical activity in vineyard soils. With this aim, soil samples (0-10 cm) from 15 vineyard soils developed on diverse parent materials were collected during winter. All soil samples were analysed for a large number of both general and specific biochemical properties. The values of all of the biochemical parameters analysed were extremely low, between 3 and 39% of the usual values obtained for native Galician soils under climax vegetation. To estimate the level of biochemical quality of vineyard soils, while avoiding the problem of comparing soils with totally different organic matter contents, a biochemical equilibrium equation was used. The results showed that vineyard soils are highly degraded soils, for which in the most extreme cases, the value of the biochemical equilibrium index was 13%, i.e. almost 8 times lower that in high quality soils such as climax soils.

Suitability of the OCDE tests to estimate contamination with 2,4-dichlorophenol of soils from Galicia (NW Spain).

The objective of the present study was to verify whether the generic reference levels (GRL) for soils contaminated with 2,4-dichlorophenol (2,4 DCP), established by Spanish legislation and published in the Real Decreto 9/2005, are accurate for Galician soils. For this, the surface horizons of seven soils under different types of land use were experimentally contaminated with different doses (between 0 and 10,000 times the GRL) of 2,4 DCP, and were then were subject to OECD toxicity test numbers 208 (root emergence and elongation) and 216 (soil nitrogen mineralization). The results obtained for the nitrogen mineralization test were difficult to interpret because they varied among soils, whereas the results of the root germination and elongation test were more coherent -- the values decreased with increasing doses of contaminant added to the soil. The results suggest that the root elongation test reflects the effect of this contaminant more clearly than the soil nitrogen mineralization test. Nevertheless, considering that in the lowest quality soils (i.e. agricultural soils containing a very low level of organic matter) contaminant doses of up to 1000 times the GRL did not affect root germination and elongation, it is clear that the GRL indicated in the relevant legislation are very low for the soils under study and that the threshold should be established taking into account the soil characteristics.

Modification of the degradative capacity of a soil artificially contaminated with diesel.

Samples of an Ah horizon from a Cambisol under oakwood vegetation were artificially contaminated with diesel (at doses of 20, 40, 80, 160 and 400 microl g(-1)) under laboratory conditions. The presence of the contaminant caused a decrease in the microbial biomass and in phosphomonoesterase, beta-glucosidase and particularly, urease activities. In contrast, the basal respiration and mineralization of nitrogen, specifically ammonification, both increased. The microorganisms that survived in the contaminated soil showed increased metabolic activity, as a result of their use of dead microorganisms as a substrate and of a lack of competition. Although the results indicate that the properties related to the degradative capacity of the soils varied differently in response to the contamination, the use of a biochemical quality index (including different biochemical properties), which was designed for estimating the degree of deterioration of the soil, revealed a clear decrease in the biochemical quality of the diesel-contaminated soils.

Retropulsion and vertigo in the Chiari malformation: case report

We describe a rare case of a 30 year-old woman with intense vertiginous sensation, lack of body balance and a tendency to fall backwards, making it necessary for two people to sustain her. The magnetic resonance imaging of the craniocervical junction evidenced tonsilar herniation at the inferior level of C1, and during the operation performed in sitting position, we observed crowding of the cerebellar tonsils at the level of C3. After the osteo-dural-neural decompression, the symptomatology remitted on the same day of the operation.

Descrevemos um caso raro de mulher de 30 anos com intensa sensação vertiginosa, desequilíbrio do corpo e tendência à queda para trás, sendo necessário o auxílio de duas pessoas para ampará-la. A ressonância nuclear magnética da junção craniovertebral evidenciou herniação tonsilar ao nível da borda inferior de C1 e, durante a operação, em posição sentada, foi observado o deslocamento craniocaudal das tonsilas cerebelares ao nível de C3. Após a descompressão ósteo-duro-neural, houve regressão da sintomatologia, no dia da operação.

Acidification-neutralization processes in a lignite mine spoil amended with fly ash or limestone.

A laboratory experiment was conducted to investigate the longterm effects of amending sulfide-rich lignite mine spoil with fly ash (originating from a coal-fired power station and largely comprised of aluminosilicates) and/or agricultural limestone. The experiment was carried out with soil moisture maintained at field capacity or alternate cycles of wetting and drying. Results obtained suggest that the principal acidification processes were oxidation of sulfide and formation of hydroxysulfate (FeOHSO4), whereas the main neutralization processes were weathering of aluminosilicates in fly ash-treated samples and dissolution of calcium carbonate in limestone-treated samples. The highest dose of limestone rapidly raised the pH of the spoil, but this increase was not maintained throughout the one-year experiment. In contrast, fly ash-treated samples showed a more sustained increase in pH, attributable to the gradual weathering of aluminosilicates. The best results (i.e., good short- and long-term neutralization) were obtained in samples treated with both fly ash and limestone. The low liming capacity of the fly ash (47.85 cmol kg(-1)) means that it must be used in large quantities, an advantage in achieving the further aim of disposing of the fly ash.