Alkaloids from Stems of Esenbeckia leiocarpa Engl. (Rutaceae) as Potential Treatment for Alzheimer Disease

Esenbeckia leiocarpa Engl. (Rutaceae), popularly known as guaranta, goiabeira, is a native tree from Brazil. Bioactivity-guided fractionation of the ethanol stems extract afforded the isolation of six alkaloids: leiokinine A, leptomerine, kokusaginine, skimmianine, maculine and flindersiamine. All isolated compounds were tested for acetyl cholinesterase inhibition, in vitro and displayed anticholinesterasic activity. The alkaloid leptomerine showed the highest activity (IC(50) = 2.5 mu M), similar to that of the reference compound galanthamine (IC(50) = 1.7 mu M). The results showed for the first time the presence of alkaloids leptomerine and skimmianine in E. leiocarpa (Engl.) with potent anticholinesterasic activity.

Polyelectrolyte-protein complexation driven by charge regulation

The interplay between the biocolloidal characteristics (especially size and charge), pH, salt concentration and the thermal energy results in a unique collection of mesoscopic forces of importance to the molecular organization and function in biological systems. By means of Monte Carlo simulations and semi-quantitative analysis in terms of perturbation theory, we describe a general electrostatic mechanism that gives attraction at low electrolyte concentrations. This charge regulation mechanism due to titrating amino acid residues is discussed in a purely electrostatic framework. The complexation data reported here for interaction between a polyelectrolyte chain and the proteins albumin, goat and bovine alpha-lactalbumin, beta-lactoglobulin, insulin, k-casein, lysozyme and pectin methylesterase illustrate the importance of the charge regulation mechanism. Special attention is given to pH congruent to pI where ion-dipole and charge regulation interactions could overcome the repulsive ion-ion interaction. By means of protein mutations, we confirm the importance of the charge regulation mechanism, and quantify when the complexation is dominated either by charge regulation or by the ion-dipole term.

Antileishmanial Activity of the Hydroalcoholic Extract of Miconia langsdorffii, Isolated Compounds, and Semi-Synthetic Derivatives

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Brazilian foreign policy: Old and new paths as regards institutional aspects, multilateralism and foreign policy towards the South

This paper emphasizes the important changes in Brazilian foreign policy after Luiz Inacio Lula da Silva took tip the power in 2002. The paper defends the idea that it is not possible to argue that there were deep changes in comparison to Cardoso's administration. However, evidence shows that new things are happening as regards the design of a more active and clear foreign action line which led to institutional changes and to more incisive multilateral paths. This results both from the political profile of the direct operators of foreign policy and the aims of lite presidential diplomacy, The hypothesis dealt with on this paper consists on the fact that Lula's administration has not fully broken with the old administration practices, however the aims of global and regional integration are being plotted more clearly and with a higher degree of activism. This becomes clear in three aspects of the Brazilian foreign policy: the institutional framework, the practice of multilateralism and the foreign policy towards the South, the three topics analyzed in this paper.

Genome Survey Sequence Analysis and Identification of Homologs of Major Surface Protease (gp63) Genes in Trypanosoma rangeli

In this study, 222 genome survey sequences were generated for Trypanosoma rangeli strain P07 isolated from an opossum (Didelphis albiventris) in Minas Gerais State, Brazil. T. rangeli sequences were compared by BLASTX (Basic Local Alignment Search Tool X) analysis with the assembled contigs of Leishmania braziliensis, Leishmania infantum, Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. Results revealed that 82% (182/222) of the sequences were associated with predicted proteins described, whereas 18% (40/222) of the sequences did not show significant identity with sequences deposited in databases, suggesting that they may represent T. rangeli-specific sequences. Among the 182 predicted sequences, 179 (80.6%) had the highest similarity with T. cruzi, 2 (0.9%) with T. brucei, and 1 (0.5%) with L. braziliensis. Computer analysis permitted the identification of members of various gene families described for trypanosomatids in the genome of T. rangeli, such as trans-sialidases, mucin-associated surface proteins, and major surface proteases (MSP or gp63). This is the first report identifying sequences of the MSP family in T. rangeli. Multiple sequence alignments showed that the predicted MSP of T. rangeli presented the typical characteristics of metalloproteases, such as the presence of the HEXXH motif, which corresponds to a region previously associated with the catalytic site of the enzyme, and various cysteine and proline residues, which are conserved among MSPs of different trypanosomatid species. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of MSP transcripts in epimastigote forms of T. rangeli.

Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's

Background: Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirao Preto (RP), a more developed city, and in 1997/98 in Sao Luis (SL), a less developed town. Methods: Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (>= 4250 g) birthweight were oversampled and estimates were corrected by weighting. Results: In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities. Conclusions: Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.

Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.

Ultra-Structural Changes at the Apical Stop Irradiated with CO(2) Laser

Objective: This study evaluated ultra-structural dentine changes at the apical stop after CO(2) laser irradiation used during biomechanical preparation. Background: Most studies evaluating the sealing efficiency of CO(2) lasers have been carried out after apical root canal resections and retro-filling procedures. Methods: Sixty human canines were prepared with #1 to #6 Largo burs. The apical stops were established at 1 mm (n = 30) and 2 mm (n = 30) from the apex. Final irrigation was performed with 1% NaOCl and 15% EDTA followed by 20 ml of distilled and deionized water. Specimens were subdivided into three subgroups (n = 10 for each stop distance): GI-no radiation (n = 20); GII-3W potency (n = 20), GIII-5W potency (n = 20). After preparation, specimens were evaluated by scanning electron microscopy, with ultra-structural changes classified according to a scoring system based on six qualitatively different outcomes. Results: Statistical analysis using the Mann-Whitney test confirmed more intense results for the specimens irradiated at 5 W potency than at 3 W (p<0.0001). The Kruskal-Wallis test indicated that when using the same potencies (3 or 5 W) at 1 and 2 mm from the apex, there were no statistically significant differences in ultra-structural changes. Conclusions: Our results showed that ultra-structural changes ranged from smear layer removal to dentine fusion. As laser potency was increased from 3 to 5 W, ultra-structural changes included extensive fused lava-like areas sealing the apical foramen.

Hepatitis B Infection Is Associated with Asymptomatic Malaria in the Brazilian Amazon

Background: Areas that are endemic for malaria are also highly endemic for hepatitis B virus (HBV) infection. Nevertheless, it is unknown whether HBV infection modifies the clinical presentation of malaria. This study aimed to address this question. Methodology and Findings: An observational study of 636 individuals was performed in Rondonia, western Amazon, Brazil between 2006 and 2007. Active and passive case detections identified Plasmodium infection by field microscopy and nested Polymerase Chain Reaction (PCR). HBV infections were identified by serology and confirmed by real-time PCR. Epidemiological information and plasma cytokine profiles were studied. The data were analyzed using adjusted multinomial logistic regression. Plasmodium-infected individuals with active HBV infection were more likely to be asymptomatic (OR: 120.13, P < 0.0001), present with lower levels of parasitemia and demonstrate a decreased inflammatory cytokine profile. Nevertheless, co-infected individuals presented higher HBV viremia. Plasmodium parasitemia inversely correlated with plasma HBV DNA levels (r=-0.6; P=0.0003). Conclusion: HBV infection diminishes the intensity of malaria infection in individuals from this endemic area. This effect seems related to cytokine balance and control of inflammatory responses. These findings add important insights to the understanding of the factors affecting the clinical outcomes of malaria in endemic regions.

Amorphous HfO(2) and Hf(1-x)Si(x)O via a melt-and-quench scheme using ab initio molecular dynamics

We have performed ab initio molecular dynamics simulations to generate an atomic structure model of amorphous hafnium oxide (a-HfO(2)) via a melt-and-quench scheme. This structure is analyzed via bond-angle and partial pair distribution functions. These results give a Hf-O average nearest-neighbor distance of 2.2 angstrom, which should be compared to the bulk value, which ranges from 1.96 to 2.54 angstrom. We have also investigated the neutral O vacancy and a substitutional Si impurity for various sites, as well as the amorphous phase of Hf(1-x)Si(x)O(2) for x=0.25, 0375, and 0.5.

Antimicrobial activity of Piper arboreum and Piper tuberculatum (Piperaceae) against opportunistic yeasts

In the scope of our ongoing research on bioactive agents from natural sources, 24 extracts and fractions obtained from Piper arboreum Aub. and Piper tuberculatum Jacq. ( Piperaceae) were screened for antifungal activity by using broth microdilution method. The current investigation reveals that P. arboreum extracts and fractions were more effective against Candida krusei and Candida parapsilosis than Cryptococcus neoformans. The growth of Candida albicans was weakly affected by all the tested extracts and fractions. The strongest effects were observed for hexane and ethyl acetate fractions from leaves of P. arboreum, with MIC values ( in mu g/ml) of 15.6 and 31.2 mu g/ml against C. krusei, respectively. Additionally, phytochemical investigation of the hexane fraction of P. arboreum leaves furnished 3 pyrrolidine amides; piperyline, 4,5-dihydropiperyline and tetrahydropiperyline, which could be responsible, at least in part for the observed antifungal activity. The most active compound, tetrahydropiperyline, displayed MIC values of 15.6 mu g/ml against C. krusei, C. parapsilosis and C. neoformans.

Amplification and diffusion of manual preference from lateralized practice in children

The effect of lateralized practice on manual preference was investigated in right-handed children. Probing tasks required reaching and grasping a pencil at distinct eccentricities in the right and left hemifields (simple), and its transportation and insertion into a small hole (complex). During practice, the children experienced manipulative tasks different from that used for probing, using the left hand only. Results showed that before practice the children used almost exclusively the right hand in the right hemifield and at the midline position. Following lateralized practice frequency of use of the left hand increased in most lateral positions. A more evident effect of lateralized practice on shift of manual preference was detected in the complex task. Implications for lateralization of behavior in a developmental timescale are discussed on the basis of the proposition of amplification and diffusion of manual preference from lateralized practice. (C) 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 723-730, 2010.

Analytical formulae for electromechanical effective properties of 3-1 longitudinally porous piezoelectric materials

A unidirectional fiber composite is considered here, the fibers of which are empty cylindrical holes periodically distributed in a transversely isotropic piezoelectric matrix, The empty-fiber cross-section is circular and the periodicity is the same in two directions at an angle pi/2 or pi/3. Closed-form formulae for all electromechanical effective properties of these 3-1 longitudinally periodic porous piezoelectric materials are presented. The derivation of such expressions is based on the asymptotic homogenization method as a limit of the effective properties of two-phase transversely isotropic parallel fiber-reinforced composites when the fibers properties tend to zero. The plane effective coefficients satisfy the corresponding Schulgasser-Benveniste-Dvorak universal type of relations, A new relation among the antiplane effective constants from the solutions of two antiplane strains and potential local problems is found. This relation is valid for arbitrary shapes of the empty-fiber cross-sections. Based on such a relation, and using recent numerical results for isotropic conductive composites, the antiplane effective properties are computed for different geometrical shapes of the empty-fiber cross-section. Comparisons with other analytical and numerical theories are presented. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Natural and human forcing in recent geomorphic change; case studies in the Rio de la Plata basin

An analysis of geomorphic system`s response to change in human and natural drivers in some areas within the Rio de la Plata basin is presented The aim is to determine whether an acceleration of geomorphic processes has taken place in recent years and, if so, to what extent it is due to natural (climate) or human (land-use) drivers Study areas of different size, socio-economic and geomorphic conditions have been selected: the Rio de la Plata estuary and three sub-basins within its watershed Sediment cores were extracted and dated ((210)Pb) to determine sedimentation rates since the end of the 19th century. Rates were compared with time series on rainfall as well as human drivers such as population, GDP, livestock load, crop area, energy consumption or cement consumption, all of them related to human capacity to disturb land surface Data on river discharge were also gathered Results obtained indicate that sedimentation rates during the last century have remained essentially constant in a remote Andean basin, whereas they show important increases in the other two, particularly one located by the Sao Paulo metropolitan area Rates in the estuary are somewhere in between It appears that there is an intensification of denudation/sedimentation processes within the basin. Rainfall remained stable or varied very slightly during the period analysed and does not seem to explain increases of sedimentation rates observed. Human drivers, particularly those more directly related to capacity to disturb land surface (GDP, energy or cement consumption) show variations that suggest human forcing is a more likely explanation for the observed change in geomorphic processes It appears that a marked increase in denudation, of a ""technological"" nature, is taking place in this basin and leading to an acceleration of sediment supply This is coherent with similar increases observed in other regions (C) 2010 Elsevier B V All rights reserved

Performance evaluation of packing materials in the removal of hydrogen sulphide in gas-phase biofilters: Polyurethane foam, sugarcane bagasse, and coconut fibre

The main objective of this work was to investigate three packing materials (polyurethane foam, sugar-cane bagasse, and coconut fibre) for biofiltration of a gaseous mixture containing hydrogen sulphide (H(2)S). Mixed cultures were obtained from two sources, aerated submerged biofilters and activated sludge, and were utilised as inoculums. Biofilters reached 100% removal efficiency after two clays of operation. The empty bed residence time was 495 for each of the biofilters. The reactors were operated simultaneously, and the inlet concentrations of H(2)S varied between 184 and 644 ppmv during the long-term continuous operation of the biofilters (100 clays). Average removal efficiencies remained above 99.3%, taking into consideration the entire period of operation. Average elimination capacities reached by the biofilters packed with polyurethane foam, coconut fibre, and sugarcane bagasse were in the range of 17.8-66.6; 18.9-68.8, and 18.7-72.9g m(-3) h(-1), respectively. Finally, we concluded that the packing materials tested in this work are appropriate for the long-term biofiltration of hydrogen sulphide. (C) 2010 Elsevier B.V. All rights reserved.