Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.

Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Influence of 60-MeV Proton-Irradiation on Standard and Strained n- and p-Channel MuGFETs

In this work the proton irradiation influence on Multiple Gate MOSFETs (MuGFETs) performance is investigated. This analysis was performed through basic and analog parameters considering four different splits (unstrained, uniaxial, biaxial, uniaxial+biaxial). Although the influence of radiation is more pronounced for p-channel devices, in pMuGFETs devices, the radiation promotes a higher immunity to the back interface conduction resulting in the analog performance improvement. On the other hand, the proton irradiation results in a degradation of the post-irradiated n-channel transistors behavior. The unit gain frequency showed to be strongly dependent on stress efficiency and the radiation results in an increase of the unit gain frequency for splits with high stress effectiveness for both cases p- and nMuGFETs.

Metal biosorption onto dry biomass of Arthrospira (Spirulina) platensis and Chlorella vulgaris: Multi-metal systems

Binary and ternary systems of Ni2+, Zn2+, and Pb2+ were investigated at initial metal concentrations of 0.5, 1.0 and 2.0 mM as competitive adsorbates using Arthrospira platensis and Chlorella vulgaris as biosorbents. The experimental results were evaluated in terms of equilibrium sorption capacity and metal removal efficiency and fitted to the multi-component Langmuir and Freundlich isotherms. The pseudo second order model of Ho and McKay described well the adsorption kinetics, and the FT-IR spectroscopy confirmed metal binding to both biomasses. Ni2+ and Zn2+ interference on Pb2+ sorption was lower than the contrary, likely due to biosorbent preference to Pb. In general, the higher the total initial metal concentration, the lower the adsorption capacity. The results of this study demonstrated that dry biomass of C. vulgaris behaved as better biosorbent than A. platensis and suggest its use as an effective alternative sorbent for metal removal from wastewater. (C) 2012 Elsevier B.V. All rights reserved.

Cationic nanoparticles for delivery of amphotericin B: preparation, characterization and activity in vitro

Abstract Background Particulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the other hand, cationic compounds and assemblies exhibit a general antimicrobial action. In this work, cationic nanoparticles built from drug, cationic lipid and polyelectrolytes are shown to be excellent and active carriers of amphotericin B against C. albicans. Results Assemblies of amphotericin B and cationic lipid at extreme drug to lipid molar ratios were wrapped by polyelectrolytes forming cationic nanoparticles of high colloid stability and fungicidal activity against Candida albicans. Experimental strategy involved dynamic light scattering for particle sizing, zeta-potential analysis, colloid stability, determination of AmB aggregation state by optical spectra and determination of activity against Candida albicans in vitro from cfu countings. Conclusion Novel and effective cationic particles delivered amphotericin B to C. albicans in vitro with optimal efficiency seldom achieved from drug, cationic lipid or cationic polyelectrolyte in separate. The multiple assembly of antibiotic, cationic lipid and cationic polyelctrolyte, consecutively nanostructured in each particle produced a strategical and effective attack against the fungus cells.

Antimicrobial and antiproliferative activities of stingless bee Melipona scutellaris geopropolis

Background Geopropolis is a type of propolis containing resin, wax, and soil, collected by threatened stingless bee species native to tropical countries and used in folk medicine. However, studies concerning the biological activity and chemical composition of geopropolis are scarce. In this study, we evaluated the antimicrobial and antiproliferative activity of the ethanolic extract of geopropolis (EEGP) collected by Melipona scutellaris and its bioactive fraction against important clinical microorganisms as well as their in vitro cytotoxicity and chemical profile. Methods The antimicrobial activity of EEGP and fractions was examined by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six bacteria strains as well as their ability to inhibit Streptococcus mutans biofilm adherence. Total growth inhibition (TGI) was chosen to assay the antiproliferative activity of EEGP and its bioactive fraction against normal and cancer cell lines. The chemical composition of M. scutellaris geopropolis was identified by reversed-phase high-performance liquid chromatography and gas chromatography–mass spectrometry. Results EEGP significantly inhibited the growth of Staphylococcus aureus strains and S. mutans at low concentrations, and its hexane fraction (HF) presented the highest antibacterial activity. Also, both EEGP and HF inhibited S. mutans biofilm adherence (p < 0.05) and showed selectivity against human cancer cell lines, although only HF demonstrated selectivity at low concentrations. The chemical analyses performed suggest the absence of flavonoids and the presence of benzophenones as geopropolis major compounds. Conclusions The empirical use of this unique type of geopropolis by folk medicine practitioners was confirmed in the present study, since it showed antimicrobial and antiproliferative potential against the cancer cell lines studied. It is possible that the major compounds found in this type of geopropolis are responsible for its properties.

Inclusive business and poverty: prospects in the Brazilian context

Inclusive business is a term currently used to explain the organizations that aim to solve social problems with efficiency and financial sustainability by means of market mechanisms. It can be said that inclusive businesses are those targeted at generating employment and income for groups with little or no market mobility, in keeping with the standards of so-called "decent jobs" and in a self-sustaining manner, i.e., generating profit for the enterprises, and establishing relationships with typical business organizations as suppliers of products and services or in the distribution of this type of production. This article discusses the different concepts found in the scientific literature on inclusive businesses. It also analyses data from a survey conducted with the audiences of Social Corporate Responsibility seminars held by FIEMG. This analysis reveals that prospects, risks and idealizations similar to those found in inclusive business theories can also be found among individuals that run social corporate responsibility projects, even if this designation is new for them. The connection between companies and poverty, especially in relation to inclusive businesses, seems full of stumbling blocks and traps in the Brazilian context.

Spatio-temporal variability of sugarcane yield efficiency in the state of São Paulo, Brazil

The objective of this work was to assess the spatial and temporal variability of sugarcane yield efficiency and yield gap in the state of São Paulo, Brazil, throughout 16 growing seasons, considering climate and soil as main effects, and socioeconomic factors as complementary. An empirical model was used to assess potential and attainable yields, using climate data series from 37 weather stations. Soil effects were analyzed using the concept of production environments associated with a soil aptitude map for sugarcane. Crop yield efficiency increased from 0.42 to 0.58 in the analyzed period (1990/1991 to 2005/2006 crop seasons), and yield gap consequently decreased from 58 to 42%. Climatic factors explained 43% of the variability of sugarcane yield efficiency, in the following order of importance: solar radiation, water deficit, maximum air temperature, precipitation, and minimum air temperature. Soil explained 15% of the variability, considering the average of all seasons. There was a change in the correlation pattern of climate and soil with yield efficiency after the 2001/2002 season, probably due to the crop expansion to the west of the state during the subsequent period. Socioeconomic, biotic and crop management factors together explain 42% of sugarcane yield efficiency in the state of São Paulo.

Yield mapping, soil fertility and tree gaps in an orange orchard

The current high competition on Citrus industry demands from growers new management technologies for superior efficiency and sustainability. In this context, precision agriculture (PA) has developed techniques based on yield mapping and management systems that recognize field spatial variability, which contribute to increase profitability of commercial crops. Because spatial variability is often not perceived the orange orchards are still managed as uniform and adoption of PA technology on citrus farms is low. Thus, the objective of the present study was to characterize the spatial variability of three factors: fruit yield, soil fertility and occurrence of plant gaps caused by either citrus blight or huanglongbing (HLB) in a commercial Valencia orchard in Brotas, São Paulo State, Brazil. Data from volume, geographic coordinates and representative area of the bags used on harvest were recorded to generate yield points that were then interpolated to produce the yield map. Soil chemical characteristics were studied by analyzing samples collected along planting rows and inter-rows in 24 points distributed in the field. A map of density of tree gaps was produced by georeferencing individual gaps and later by counting the number of gaps within 500 m² cells. Data were submitted to statistical and geostatistical analyses. A t test was used to compare means of soil chemical characteristics between sampling regions. High variation on yield and density of tree gaps was observed from the maps. It was also demonstrated overlapping regions of high density of plant absence and low fruit yield. Soil fertility varied depending on the sampling region in the orchard. The spatial variability found on yield, soil fertility and on disease occurrence demonstrated the importance to adopt site specific nutrient management and disease control as tools to guarantee efficiency of fruit production.

Gene expression and phenotypic traits of Aggregatibacter actinomycetemcomitans in response to environmental changes

Background and Objective: Periodontopathogens experience several challenges in the oral cavity that may influence their transcription profile and resulting phenotype. This study evaluated the effect of environmental changes on phenotype and gene expression in a serotype b Aggregatibacter actinomycetemcomitans isolate. Material and Methods: Cultures in early exponential phase and at the start of stationary growth phase in microaerophilic and anaerobic atmospheres were evaluated. Cell hydrophobic properties were measured by adherence to n-hexadecane; in addition, adhesion to, and the ability to invade, KB cells was evaluated. Relative transcription of 12 virulence-associated genes was determined by real-time reverse transcritption quantitative PCR. Results: The culture conditions tested in this study were found to influence the phenotypic and genotypic traits of A. actinomycetemcomitans. Cells cultured in microaerophilic conditions were the most hydrophobic, reached the highest adhesion efficiency and showed up-regulation of omp100 (which encodes an adhesion) and pga (related to polysaccharide synthesis). Cells grown anaerobically were more invasive to epithelial cells and showed up-regulation of genes involved in host-cell invasion or apoptosis induction (such as apaH, omp29, cagE and cdtB) and in adhesion to extracellular matrix protein (emaA). Conclusion: Environmental conditions of different oral habitats may influence the expression of factors involved in the binding of A. actinomycetemcomitans to host tissues and the damage resulting thereby, and thus should be considered in in-vitro studies assessing its pathogenic potential.