Investigation on the Anticonvulsant Potential of Luteolin and Micronized Luteolin in Adult Zebrafish (Danio rerio)

Neurochemical Research - Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have...     

Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation

Background

Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.

Results

We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.

Conclusions

These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.

     

A feedforward model for the formation of a grid field where spatial information is provided solely from place cells

Grid cells (GCs) in the medial entorhinal cortex (mEC) have the property of having their firing activity spatially tuned to a regular triangular lattice. Several theoretical models for grid field formation have been proposed, but most assume that place cells (PCs) are a product of the grid cell system. There is, however, an alternative possibility that is supported by various strands of experimental data. Here we present a novel model for the emergence of gridlike firing patterns that stands on two key hypotheses: (1) spatial information in GCs is provided from PC activity and (2) grid fields result from a combined synaptic plasticity mechanism involving inhibitory and excitatory neurons mediating the connections between PCs and GCs. Depending on the spatial location, each PC can contribute with excitatory or inhibitory inputs to GC activity. The nature and magnitude of the PC input is a function of the distance to the place field center, which is inferred from rate decoding. A biologically plausible learning rule drives the evolution of the connection strengths from PCs to a GC. In this model, PCs compete for GC activation, and the plasticity rule favors efficient packing of the space representation. This leads to gridlike firing patterns. In a new environment, GCs continuously recruit new PCs to cover the entire space. The model described here makes important predictions and can represent the feedforward connections from hippocampus CA1 to deeper mEC layers.     

Influence of Soil Chemistry and Plant Physiology in the Phytoremediation of Cu,Mn, and Zn

Different anthropogenic sources of metals can result from agricultural, industrial, military, mining and urban activities that contribute to environmental pollution. Plants can be grown for phytoremediation to remove or stabilize contaminants in water and soil. Copper (Cu), manganese (Mn) and zinc (Zn) are trace essential metals for plants, although their role in homeostasis in plants must be strictly regulated to avoid toxicity. In this review, we summarize the processes involved in the bioavailability, uptake, transport and storage of Cu, Mn and Zn in plants. The efficiency of phytoremediation depends on several factors including metal bioavailability and plant uptake, translocation and tolerance mechanisms. Soil parameters, such as clay fraction, organic matter content, oxidation state, pH, redox potential, aeration, and the presence of specific organisms, play fundamental roles in the uptake of trace essential metals. Key processes in the metal homeostasis network in plants have been identified. Membrane transporters involved in the acquisition, transport and storage of trace essential metals are reviewed. Recent advances in understanding the biochemical and molecular mechanisms of Cu, Mn and Zn hyperaccumulation are described. The use of plant-bacteria associations, plant-fungi associations and genetic engineering has opened a new range of opportunities to improve the efficiency of phytoremediation. The main directions for future research are proposed from the investigation of published results.     

Patterns of Adherence to and Compliance with the Portuguese Smoke-Free Law in the Leisure-Hospitality Sector

Background

In 2008, the Portuguese smoke-free law came into effect including partial bans in the leisure-hospitality (LH) sector. The objective of the study is to assess the prevalence of smoking control policies (total ban, smoking permission and designated smoking areas) adopted by the LH sector in Portugal. The levels of noncompliance with each policy are investigated as well as the main factors associated with smoking permission and noncompliance with the law.

Methods

Cross-sectional study conducted between January 2010 and May 2011. A random sample of venues was selected from the Portuguese LH sector database, proportionally stratified according to type, size and geographical area. All venues were assessed in loco by an observer. The independent effects of venues'' characteristics on smoking permission and the level of noncompliance with the law were explored using logistic regression.

Results

Overall, 1.412 venues were included. Total ban policy was adopted by 75.9% of venues, while 8.4% had designated smoking areas. Smoking ban was more prevalent in restaurants (85.9%). Only 29.7% of discos/bars/pubs opted for complete ban. Full or partial smoking permission was higher in discos/bar/pubs (OR = 7.37; 95%CI 4.87 to 11.17). Noncompliance with the law was higher in venues allowing smoking and lower in places with complete ban (33.6% and 7.6% respectively, p<0.001). Discos/bars/pubs with full smoking permission had the highest level of noncompliance (OR = 3.31; 95%CI 1.40 to 7.83).

Conclusions

Our findings show a high adherence to smoking ban policy by the Portuguese LH sector. Nonetheless, one quarter of the venues is fully or partially permissive towards smoking, with the discos/bars/pubs considerably contributing to this situation. Venues with smoking permission policies were less compliant with the legislation. The implementation of a comprehensive smoke-free law, without any exceptions, is essential to effectively protect people from the second hand smoke.     

Characterization of rumen bacterial strains isolated from enrichments of rumen content in the presence of propolis

Propolis presents many biological properties, including antibacterial activities, and has been proposed as an additive in ruminant nutrition. Twenty bacterial strains, previously isolated from enrichments of Brazilian cow rumen contents in the presence of different propolis extracts (LLOS), were characterized using phenotyping and 16S rRNA identification. Seven strains were assigned to Streptococcus sp., most likely S. bovis, and were all degrading starch. One amylolytic lactate-utilizing strain of Selenomonas ruminantium was also found. Two strains of Clostridium bifermentans were identified and showed proteolytic activity. Two strains were assigned to Mitsuokella jalaludinii and were saccharolytic. One strain belonged to a Bacillus species and seven strains were affiliated with Escherichia coli. All of the 20 strains were able to use many sugars, but none of them were able to degrade the polysaccharides carboxymethylcellulose and xylans. The effect of three propolis extracts (LLOS B1, C1 and C3) was tested on the in vitro growth of four representative isolates of S. bovis, E. coli, M. jalaludinii and C. bifermentans. The growth of S. bovis, E. coli and M. jalaludinii was not affected by the three propolis extracts at 1 mg ml^?1. C. bifermentans growth was completely inhibited at this LLOS concentration, but this bacterium was partially resistant at lower concentrations. LLOS C3, with the lower concentration of phenolic compounds, was a little less inhibitory than B1 and C1 on this strain.     

H-2 complex influences cytokine gene expression in Leishmania infantum-infected macrophages

This work aims to study the influence of H-2 locus in the control of Leishmania infantum infection by evaluating whether cytokine responses by host macrophages of different H-2 haplotype are differentially regulated, either induced or actively impaired during parasite growth and replication. This study shows that macrophages of "non-cure" phenotype (H-2(d)) are more susceptible to infection with virulent L. infantum promastigotes. Virulent parasites lead to impaired IL-12 and inhibited TNF-alpha expression. The degree of parasite virulence is an important contributing factor to differences detected in cytokine expression. Virulent parasites also induced TGF-beta, a deactivating cytokine that is known to suppress Th-1 type responses, thus allowing the parasite to subvert antimicrobial activity and increase its chances of survival. Depending on specific host haplotype, cells differentially respond to infection since TNF-alpha expression is inhibited and TGF-beta is enhanced by macrophages of "non-cure" phenotype, thus perhaps determining their degree of susceptibility in this strain of mice.     

Development and validation of a RP-HPLC method for quantification of isoflavone aglycones in hydrolyzed soy dry extracts

Isoflavones are widely used as an alternative treatment to hormone replacement therapy and also for prevention of several chronic diseases, including cancers. Genistein, daidzein and glycitein are the most abundant isoflavone aglycones found in soy extracts, where they also occur as glycosides. This paper describes the development and validation of an isocratic reversed-phase HPLC (RP-HPLC) method for the analysis of isoflavone aglycones, released after acid hydrolysis of soy dry extracts, used as pharmaceutical raw material. The quantification was carried out in a C(18) endcapped column, using a mobile phase composed of 0.1% acetic acid and methanol (52:48), at a flow rate of 1.0 ml/min and diode array detection (DAD) at 254 nm. The method showed to be linear (r(2)>0.99), precise (R.S.D.<2%), accurate (recovery of 98.88% for daidzein and 98.12% for genistein), robust and specific.