Proteome analysis of snake venom toxins: pharmacological insights

Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

Synganglion histology in different stages of Rhipicephalus sanguineus ticks (Acari: Ixodidae)

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

Collagen fibers in human prostatic lesions: histochemistry and anisotropies

The present study focuses on establishing patterns of collagen fibers distribution in prostatic nodular hyperplasia and adenocarcinomas, in comparison with the normal tissue. Sections of prostatic transurethral resection were subjected to Gömöri's method for collagen fibers and reticulin and analyzed under ordinary and polarized light microscopy. Controls and hyperplastic regions present collagen fibers with variable thickness that run in different directions, establishing a tridimensional network. These fibers exhibit birefringence and dichroism thus demonstrating their fibrillar integrity. On the other hand, increased variability in collagen fiber distribution and anisotropical properties occur in adenocarcinomas evaluated in accordance with the Gleason's score. In some of their areas, a well-defined collagen network delimitates the base of transformed epithelial cells whereas in other areas the collagen fibers are disorganized and do not establish a boundary between the epithelial structures and the stroma. In these areas, collagen is found in the stroma. It was also observed that adenocarcinoma tumor cells rest on a scaffold of thin and dendritic collagen fibers. Collagen fibers of the prostatic stroma of the adenocarcinomas may show a modification in arrangement and fibrillar compactness. In prostatic nodular hyperplasia, there is no change in collagen molecular integrity, since collagen affinity for silver and collagen birefringence are similar to controls. In adenocarcinoma with high dedifferentiation degree, thin and branched strongly argyrophilic and birefringent collagen fibers are detected in regions of cell proliferation. In the adjacent stroma, hyaline plaques are indicative of matrix degradation or remodellation.

Porous hydroxyapatite scaffolds by polymer sponge method

This study aimed to develop porous hydroxyapatite scaffold for bone regeneration using the replica of the polymeric sponge technique. Polyurethane sponges were used with varying densities to obtain the scaffolds. The results indicate the porous HA scaffolds developed in this study as potential materials for application as bone substitutes to have high porosity (> 70%), chemical composition, interconnectivity and pore sizes appropriate to the bone regeneration.

Effect of brushing with conventional versus whitening dentifrices on surface roughness and biofilm formation of dental ceramics

The aim of this study was to evaluate the effect of conventional and whitening dentifrices on the weight loss, surface roughness, and early in situ biofilm formation on the surface of dental ceramics. Standardized feldspar ceramic specimens (Vita VM7 and Vita VM13) were submitted to the following experimental conditions: no brushing; brushing without a dentifrice; brushing with a conventional dentifrice; and brushing with a whitening dentifrice. A brushing machine was used to simulate brushing. The mass and surface roughness of all specimens from the test groups were evaluated prior to and after brushing. Ten participants used an oral device for eight hours to evaluate the biofilm formed in situ on the specimens. Scanning electron microscopy was used for qualitative and quantitative analysis of the biofilm. ANOVA and Tukey tests were used to analyze the results of weight loss, surface roughness, and presence of bacteria. A one-way Kruskal-Wallis test was used for bacterial colonization results. For both ceramics, brushing with a whitening dentifrice resulted in weight loss that was significantly greater when compared to brushing without a dentifrice or with a conventional dentifrice. Increased surface roughness was noticed on VM13 ceramic samples with both dentifrices, whereas only conventional dentifrice had a significant effect on the surface roughness of VM7 samples. For both VM7 and VM13, no difference was found between the experimental conditions with regard to the presence or number of bacteria. Cocci and short rods were the predominant microbial morphotypes. Granular or fibrillar acellular material partially covered the specimens. Brushing with a whitening dentifrice resulted in significant weight loss of ceramic restorations, while brushing with both conventional and whitening dentifrices can roughen ceramic surfaces. The increase in roughness was not clinically significant to contribute to increased biofilm formation.

Xenograft enriched with autologous bone marrow in inlay reconstructions: A tomographic and histomorphometric study in rabbit calvaria

Objective. The aim of this study was to evaluate the bone healing after the usage of a scaffold enriched with bone marrow. Study Design. Ten rabbits were divided into 2 groups of 5 animals. Bilateral 12 mm diameter defects were created in the parietal bones. In control group Bio-Oss were inserted in both defects and, in experimental group, Bio-Oss enriched with autologous bone marrow were inserted in both defects. In these two groups, one of the calvarial defects was covered with Bio-Gide. The rabbits were sacrified 8 weeks after surgery and both CT and histomorphometric analysis were done. Results. The CT showed a lower remaining defect area in the experimental group covered with Bio-Gide when compared with control group, with and without Bio-Gide. The histomorphometrics showed no difference between groups regarding the non-vital mineralized tissue area. For vital mineralized tissue area, the experimental group covered with Bio-Gide obtained a higher percentage area when compared with control group, with and without Bio-Gide. For non-mineralized tissue area, the experimental group covered with Bio-Gide obtained a lower percentage area when compared with control group, with and without Bio-Gide. Conclusion. Both autologous bone marrow and membrane can contribute to the enhancement of bone healing. Copyright © 2012 Marcelo de Oliveira e Silva et al.

Bionanocomposites from electrospun PVA/pineapple nanofibers/Stryphnodendron adstringens bark extract for medical applications

Tissue engineering has been defined as an interdisciplinary field that applies the principles of engineering and life sciences for the development of biological substitutes to restore, maintain or improve tissue function. This area is always looking for new classes of degradable biopolymers that are biocompatible and whose activities are controllable and specific, more likely to be used as cell scaffolds, or in vitro tissue reconstruction. In this paper, we developed a novel bionanocomposite with homogeneous porous distribution and prospective natural antimicrobial properties by electrospinning technique using Stryphodedron barbatimao extract (Barbatimão). SEM images showed equally distribution of nanofibres. DSC and TGA showed higher thermal properties and change crystallinity of the developed bionanocomposite mainly because these structural modification. © 2012 Elsevier B.V.

Synthesis, cytotoxicity and in vitro antileishmanial activity of naphthothiazoles

The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp., which threatens millions of people worldwide. Current treatments exhibit high toxicity, and there is no vaccine available. The need for new lead compounds with leishmanicidal activity is urgent. Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi-synthetic heterocycles with antileishmanial activity. We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages. Furthermore, the compounds were not cytotoxic to macrophages at fivefold higher concentrations than the EC50 for promastigotes. All molecules fulfilled Lipinski's Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics. The potent and selective activity of semi-synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2-amino-naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo. © 2013 John Wiley & Sons A/S.

Structural and functional studies with mytoxin II from Bothrops moojeni reveal remarkable similarities and differences compared to other catalytically inactive phospholipases A2-like

Lys49-phospholipases A2 (Lys49-PLA2s) are proteins found in bothropic snake venoms (Viperidae family) and belong to a class of proteins which presents a phospholipase A2 scaffold but are catalytically inactive. These proteins (also known as PLA2s-like toxins) exert a pronounced local myotoxic effect and are not neutralized by antivenom, being their study relevant in terms of medical and scientific interest. Despite of the several studies reported in the literature for this class of proteins only a partial consensus has been achieved concerning their functional-structural relationships. In this work, we present a comprehensive structural and functional study with the MjTX-II, a dimeric Lys49-PLA2 from Bothrops moojeni venom which includes: (i) high-resolution crystal structure; (ii) dynamic light scattering and bioinformatics studies in order to confirm its biological assembly; (iii) myographic and electrophysiological studies and, (iv) comparative studies with other Lys49-PLA2s. These comparative analyses let us to get important insights into the role of Lys122 amino acid, previously indicated as responsible for Lys49-PLA2s catalytic inactivity and added important elements to establish the correct biological assembly for this class of proteins. Furthermore, we show two unique sequential features of MjTX-II (an amino acid insertion and a mutation) in comparison to all bothropic Lys49-PLA2s that lead to a distinct way of ligand binding at the toxin's hydrophobic channel and also, allowed the presence of an additional ligand molecule in this region. These facts suggest a possible particular mode of binding for long-chain ligands that interacts with MjTX-II hydrophobic channel, a feature that may directly affect the design of structure-based ligands for Lys49-PLA2s. © 2013 Elsevier Ltd.

Transcript finishing initiative: contribuição do laboratório IL2

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Histomorfometria das fibras colágenas e das fibras do sistema elástico da queilite actínica e sua relação com os níveis de atipia

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento de métodos de cultivo de Gluconacetobacter xylinus para obtenção de compósitos à base de celulose bacteriana e colágeno tipo I adicionado in situ

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

Estruturação ex-vivo de vasos sanguíneos a partir da diferenciação de células tronco de coelhos

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Avaliação da viabilidade do selante de fibrina derivado de veneno de serpente como arcabouço biológico para células-tronco mesenquimais de medula óssea de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação de novas propostas em arcabouços tridimencionais (3D) para cultura de células-tronco mesenquinas e condogênese

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)