Crystal structure of a dimeric Ser49 PLA(2)-like myotoxic component of the Vipera ammodytes meridionalis venomics reveals determinants of myotoxicity and membrane damaging activity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A partial least squares and principal component regression study of quinone compounds with trypanocidal activity

A quantitative structure-activity relationship (QSAR) study of 19 quinone compounds with trypanocidal activity was performed by Partial Least Squares (PLS) and Principal Component Regression (PCR) methods with the use of leave-one-out crossvalidation procedure to build the regression models. The trypanocidal activity of the compounds is related to their first cathodic potential (Ep(c1)). The regression PLS and PCR models built in this study were also used to predict the Ep(c1) of six new quinone compounds. The PLS model was built with three principal components that described 96.50% of the total variance and present Q(2) = 0.83 and R-2 = 0.90. The results obtained with the PCR model were similar to those obtained with the PLS model. The PCR model was also built with three principal components that described 96.67% of the total variance with Q(2) = 0.83 and R-2 = 0.90. The most important descriptors for our PLS and PCR models were HOMO-1 (energy of the molecular orbital below HOMO), Q4 (atomic charge at position 4), MAXDN (maximal electrotopological negative difference), and HYF (hydrophilicity index).

Poly(Lactide-co-Glycolide) Nanocapsules Containing Benzocaine: Influence of the Composition of the Oily Nucleus on Physico-Chemical Properties and Anesthetic Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Platelet-rich plasma stimulates cytokine expression and alkaline phosphatase activity in osteoblast-derived osteosarcoma cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation

Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats or in the working heart-brainstem preparation (WHBP) produces: (a) a sympathoexcitatory/pressor response; (b) bradycardia; and (c) an increase in the frequency of breathing. Our main aim was to evaluate neurotransmitters involved in mediating the sympathoexcitatory component of the chemoreflex within the nucleus tractus solitarii (NTS). In previous studies in conscious rats, the reflex bradycardia, but not the pressor response, was reduced by antagonism of either ionotropic glutamate or purinergic P2 receptors within the NTS. In the present study we evaluated a possible dual role of both P2 and NMDA receptors in the NTS for processing the sympathoexcitatory component (pressor response) of the chemoreflex in awake rats as well as in the WHBP. Simultaneous blockade of ionotropic glutamate receptors and P2 receptors by sequential microinjections of kynurenic acid (KYN, 2 nmol (50 nl)(-1)) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS, 0.25 nmol (50 nl)(-1)) into the commissural NTS in awake rats produced a significant reduction in both the pressor (+38 +/- 3 versus +8 +/- 3 mmHg) and bradycardic responses (-172 +/- 18 versus -16 +/- 13 beats min(-1); n = 13), but no significant changes in the tachypnoea measured using plethysmography (270 +/- 30 versus 240 +/- 21 cycles min(-1), n = 7) following chemoreflex activation in awake rats. Control microinjections of saline produced no significant changes in these reflex responses. In WHBP, microinjection of KYN (2 nmol (20 nl)(-1)) and PPADS (1.6 nmol (20 nl)(-1)) into the commissural NTS attenuated significantly both the increase in thoracic sympathetic activity (+52 +/- 2% versus +17 +/- 1%) and the bradycardic response (-151 +/- 17 versus -21 +/- 3 beats min(-1)) but produced no significant changes in the increase of the frequency of phrenic nerve discharge (+0.24 +/- 0.02+0.20 +/- 0.02 Hz). The data indicate that combined microinjections of PPADS and KYN into the commissural NTS in both awake rats and the WHBP are required to produce a significant reduction in the sympathoexcitatory response (pressor response) to peripheral chemoreflex activation. We conclude that glutamatergic and purinergic mechanisms are part of the complex neurotransmission system of the sympathoexcitatory component of the chemoreflex at the level of the commissural NTS.

The 20S proteasome alpha(5) subunit of Arabidopsis thaliana carries an RNase activity and interacts in planta with the Lettuce mosaic potyvirus HcPro protein

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anthelmintic activity of Cymbopogon martinii, Cymbopogon schoenanthus and Mentha piperita essential oils evaluated in four different in vitro tests

Anthelmintic resistance is a worldwide concern in small ruminant industry and new plant-derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmental stages of trichostrongylids from sheep naturally infected (95% Haemonchus contortus and 5% Trichostrogylus spp.) through the egg hatch assay (EHA), larval development assay (LDA), larval feeding inhibition assay (LFIA), and the larval exsheathment assay (LEA). The major constituent of the essential oils, quantified by gas chromatography for M. piperita oil was menthol (42.5%), while for C. martinii and C. schoenanthus the main component was geraniol (81.4% and 62.5%, respectively). In all in vitro tests C. schoenanthus essential oil had the best activity against ovine trichostrongylids followed by C. martini, while M. piperita presented the least activity. Cymbopogon schoenanthus essential oil had LC(50) value of 0.045 mg/ml in EHA, 0.063 mg/ml in LDA, 0.009 mg/ml in LFIA, and 24.66 mg/ml in LEA. The anthelmintic activity of essential oils followed the same pattern in all in vitro tests, suggesting C. schoenanthus essential oil could be an interesting candidate for nematode control, although in vivo studies are necessary to validate the anthelmintic properties of this oil. (C) 2011 Elsevier B.V. All rights reserved.

Antioxidant activity, fatty acid profile and tocopherols of Tamarindus indica L. seeds

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The structure of a native L-amino acid oxidase, the major component of the Vipera ammodytes ammodytes venomic, reveals dynamic active site and quaternary structure stabilization by divalent ions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy

In order to characterize the cellular component of the polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland, a morphological and immunohistochemical study was carried out. Thirty cases of PLGA were studied by light microscopy and immunohistochemistry and five cases by transmission electron microscopy (TEM). The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated through the streptavidin-biotin method. The majority of tumor cells stained for vimentin, CKs 8,18 and 7. CK 14 was positive in most cells of the papillary and trabecular sub-types. Although the expression of CKs 8,18 and 14 varied among the tumors sub-types, a straight relationship between each histologic pattern and the CK expression could not be delineated. MSA was reactive in only three tumors while CKs 10 and 13 were not detected in any tumor studied. The absence of MSA and the expression of CKs 8,18 and 7, in most of the tumor cells, lead to the hypothesis that myoepithelial cells are not the major cellular component of the PLGA. TEM revealed cells exhibiting microvilli and variable amounts of secretory granules, some of them suggesting an excretory activity. The presence of CKs 8, 18 and 7, added to the secretory granules, indicates that PLGA originates from cells located at the acinar-intercalated duct junction. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

A structure-activity relationship study of quinone compounds with trypanocidal activity

A set of 25 quinone compounds with anti-trypanocidal activity was studied by using the density functional theory (DFT) method in order to calculate atomic and molecular properties to be correlated with the biological activity. The chemometric methods principal component analysis (PCA), hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA), Kth nearest neighbor (KNN) and soft independent modeling of class analogy (SIMCA) were used to obtain possible relationships between the calculated descriptors and the biological activity studied and to predict the anti-trypanocidal activity of new quinone compounds from a prediction set. Four descriptors were responsible for the separation between the active and inactive compounds: T-5 (torsion angle), QTS1 (sum of absolute values of the atomic charges), VOLS2 (volume of the substituent at region B) and HOMO-1 (energy of the molecular orbital below HOMO). These descriptors give information on the kind of interaction that occurs between the compounds and the biological receptor. The prediction study was done with a set of three new compounds by using the PCA, HCA, SDA, KNN and SIMCA methods and two of them were predicted as active against the Trypanosoma cruzi. (c) 2005 Elsevier SAS. All rights reserved.

Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 mug ml(-1)) or F1 (100 and 200 mug ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. on the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.

Anti-inflammatory intestinal activity of Abarema cochliacarpos (Gomes) Barneby & Grimes in TNBS colitis model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluating of the activity antioxidant and fatty acids profile of lychee seeds (Litchi chinensis SONN.)

Purpose: The purpose of this paper is to characterize lychee seeds regarding their centesimal composition, and also to evaluate their antioxidant potential and fatty acid profile. Design/methodology/approach: To obtain the extract, dehydrated and grinded seeds were extracted with ethyl alcohol for 30 min, at a proportion of 1:3 of seeds:ethyl alcohol, under continuous agitation, at room temperature. Afterwards, the mixture was filtered and the supernatant subjected to a rotoevaporator at 40oC aiming to determine, by direct weighing, the extract dry matter yield. Findings: The largest found values went to the total carbohydrates (72.75 percent). In the oil from the lychee seeds there was a high percentage of unsaturated fatty acids, the main component being linoleic, considered an essential fatty acid. Research limitations/implications: Implies the identification of compounds biativos extracted from seeds of tropical and subtropical fruits, and to prevent certain types of diseases. Originality/value: The article tries to identify new source of phenolic compounds extracted from fruit. © Emerald Group Publishing Limited.

Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting the biological activity of novel peptides from venoms and hemolymph

When searching for prospective novel peptides, it is difficult to determine the biological activity of a peptide based only on its sequence. The trial and error approach is generally laborious, expensive and time consuming due to the large number of different experimental setups required to cover a reasonable number of biological assays. To simulate a virtual model for Hymenoptera insects, 166 peptides were selected from the venoms and hemolymphs of wasps, bees and ants and applied to a mathematical model of multivariate analysis, with nine different chemometric components: GRAVY, aliphaticity index, number of disulfide bonds, total residues, net charge, pI value, Boman index, percentage of alpha helix, and flexibility prediction. Principal component analysis (PCA) with non-linear iterative projections by alternating least-squares (NIPALS) algorithm was performed, without including any information about the biological activity of the peptides. This analysis permitted the grouping of peptides in a way that strongly correlated to the biological function of the peptides. Six different groupings were observed, which seemed to correspond to the following groups: chemotactic peptides, mastoparans, tachykinins, kinins, antibiotic peptides, and a group of long peptides with one or two disulfide bonds and with biological activities that are not yet clearly defined. The partial overlap between the mastoparans group and the chemotactic peptides, tachykinins, kinins and antibiotic peptides in the PCA score plot may be used to explain the frequent reports in the literature about the multifunctionality of some of these peptides. The mathematical model used in the present investigation can be used to predict the biological activities of novel peptides in this system, and it may also be easily applied to other biological systems. © 2011 Elsevier Inc.