Chaetoglobosins produced by Chaetomium globosum, endophytic fungus found in association with Viguiera robusta Gardn (Asteraceae)

Endophytes live in association with host plants during all or part of their life cycle without causing any apparent disease. They are considered outstanding and underexploited sources of novel bioactive compounds. Chaetomium globosum was isolated as an endophytic fungus from the healthy leaves of Viguiera robusta. C.globosum is a remarkable producer of chaetoglobosins, which are typically cytotoxic. In this work, chaetoglobosins B (1), D (2) and E (3) have been produced by the endophytic C. globosum strain. Chaetoglobosin B was evaluated against Jurkat (leukemia) and B16F10 (melanoma) tumoral cells and showed 89.55% and 57.10% of inhibition at 0.1 mg mL-1, respectively. Chaetoglobosin B also showed weak antibacterial activity against Staphylococcus aureus (MIC 120 µg/mL) and Escherichia coli (MIC 189 µg/mL).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Diabetes immersion training as teaching method to medical practitioners

Este estudo avaliou a eficácia do método de ensino teórico e prático sobre diabetes e a atitude de profissionais médicos quanto à realização de controle glicêmico intensivo. Participaram de um curso de imersão em diabetes, com dois dias de duração, 48 médicos-residentes de clínica médica ou endocrinologia. Os participantes receberam treinamento de monitorização de glicemia capilar, técnicas de aplicação de insulina e contagem de carboidratos, sendo orientados a se portarem como diabéticos e a seguir prescrição médica individual. Foram avaliados através de questionários. No questionário de conhecimentos, observou-se um aumento significante de 12% no índice de acertos entre o início e o final do curso (61,2% e 73,2%, respectivamente, com p < 0,0001). Antes do curso, 70,8% dos participantes diziam ter dificuldades na contagem de carboidratos e 89,6%, na automonitorização glicêmica. Após a experiência prática, 82,9% dos participantes encontraram dificuldades na realização de contagem de carboidratos e 80,8%, na automonitorização; 40,4% fizeram uso de todas as medicações prescritas e 36,1% monitorizaram todas as glicemias. Os resultados deste estudo mostram que esse tipo de curso é eficaz para a aquisição de conhecimentos e contribui com a sensibilização do profissional médico quanto às dificuldades cotidianas enfrentadas pelo portador de diabetes melito na aderência às recomendações.This study evaluated the effectiveness of theoretical and practical teaching method in diabetes and doctors' position about feasibility of intensive blood glucose control. Forty-eight internal medicine or endocrinology residents participated in a two-day diabetes immersion course. The participants received training on self-blood glucose monitoring, techniques of insulin administration and carbohydrate counting. They were also instructed to behave as patients with diabetes and to follow individual medical prescription. They were assessed through questionnaires. In knowledge assessment, a significant increase of 12% was observed between the beginning and the end of the course (61.2% and 73.2%, respectively, with p < 0.0001). Before the course, 70.8% and 89.6% of the participants believed there were complications in performing carbohydrate counting and blood glucose monitoring, respectively. After the experience, 82.9% of them had difficulties in carbohydrate counting and 80.8% in self-monitoring; 40.4% took all medications prescribed and 36.1% monitored blood glucose correctly. These results show that the methodology of this course is an effective way to disseminate knowledge and that it contributes to doctors becoming more sensitive to daily problems faced by patients with diabetes melito concerning the acceptance of medical recommendations

Characterization of two-year progression of neurodegeneration in different risk phenotypes of diabetic retinopathy

To characterize the two-year progression of neurodegeneration in different diabetic retinopathy (DR) risk phenotypes in type 2 diabetes.info:eu-repo/semantics/publishedVersio

Matemática no percurso formativo de futuros professores dos anos iniciais a

Considering the importance of History of Mathematics (HM) in the Mathematics teaching and the need for its approach in the initial training of teachers, this study aims to: characterize the use of HM in the educational trajectory of future teachers (FT) in basic and secondary levels; describe their training in HM in the Basic Education (BE) degree; and identify these FT's conceptions about the importance of using HM in Mathematics teaching. In this study, 63 female FTs participated in this study, graduated in BE in Portuguese institutions and starting a professional master's degree. Data collection resulted from the application of a questionnaire, with two parts: Teaching/Training with/in HM; and Conceptions about the contributions of HM to Mathematics teaching. The results reveal that 68% of the FT consider non-existent, or limited to episodic moments, the use of HM in their Mathematics classes during their primary and secondary education; FT also consider that training in HM during the BE course was frequent (52%) or solid (17%). The use of HM is evaluated positively because facilitates the understanding of the contents, illustrate the usefulness, importance and connections of Mathematics, and allows different approaches and developing transversal skills.info:eu-repo/semantics/publishedVersio

Systematic comparison of the effects of Alpha-synuclein mutations on its oligomerization and aggregation

Copyright: © 2014 Lázaro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease. However, the precise contribution of ASYN to neuronal dysfunction and death is unclear. There is intense debate about the nature of the toxic species of ASYN and little is known about the molecular determinants of oligomerization and aggregation of ASYN in the cell. In order to clarify the effects of different mutations on the propensity of ASYN to oligomerize and aggregate, we assembled a panel of 19 ASYN variants and compared their behaviour. We found that familial mutants linked to PD (A30P, E46K, H50Q, G51D and A53T) exhibited identical propensities to oligomerize in living cells, but had distinct abilities to form inclusions. While the A30P mutant reduced the percentage of cells with inclusions, the E46K mutant had the opposite effect. Interestingly, artificial proline mutants designed to interfere with the helical structure of the N-terminal domain, showed increased propensity to form oligomeric species rather than inclusions. Moreover, lysine substitution mutants increased oligomerization and altered the pattern of aggregation. Altogether, our data shed light into the molecular effects of ASYN mutations in a cellular context, and established a common ground for the study of genetic and pharmacological modulators of the aggregation process, opening new perspectives for therapeutic intervention in PD and other synucleinopathies.This work was supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB).info:eu-repo/semantics/publishedVersio

Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia

A total of 39 endophytic fungi have been isolated from Viguiera arenaria and Tithonia diversifolia, both collected in São Paulo State, Brazil. The isolates were identified based on their ribosomal DNA sequences. The ethyl acetate (EtOAc) extracts of all endophytic fungi were evaluated for their antimicrobial, antiparasitic and antitumoral activity. Antimicrobial screening was conducted using an agar diffusion assay against three pathogenic microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. Antiparasitic activity was determined by enzymatic inhibition of gGAPDH of Trypanosoma cruzi and adenine phosphorybosiltransferase (APRT) of Leishmania tarentolae. Antitumoral activity was tested against human T leukemia cells by the Mosmann colorimetric method. All extracts showed activity in at least one assay: 79.5% of the extracts were cytotoxic against leukemia cells, 5.1% of the extracts were active against S. aureus, 25.6% against E. coli and 64.1% against Candida albicans. Only one extract showed promising results in the inhibition of parasitic enzymes gGAPDH (95.0%) and three were found to inhibit APRT activity. The cytotoxic extract produced by the strain VA1 (Glomerella cingulata) was fractionated and yielded nectriapyrone and tyrosol. Nectriapyrone showed relevant cytotoxic activity against both human T leukemia and melanoma tumor cell lines.FAPESP 03/07535-5FAPESP 04/07935-6CAPE

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Unexpectedly long incubation period of Plasmodium vivax malaria, in the absence of chemoprophylaxis, in patients diagnosed outside the transmission area in Brazil

<p>Abstract</p> <p>Background</p> <p>In 2010, Brazil recorded 3343,599 cases of malaria, with 99.6% of them concentrated in the Amazon region. <it>Plasmodium vivax </it>accounts for 86% of the cases circulating in the country. The extra-Amazonian region, where transmission does not occur, recorded about 566 cases imported from the Amazonian area in Brazil and South America, from Central America, Asia and African countries. Prolonged incubation periods have been described for <it>P. vivax </it>malaria in temperate climates. The diversity in essential biological characteristics is traditionally considered as one possible explanation to the emergence of relapse in malaria and to the differences in the duration of the incubation period, which can also be explained by the use of chemoprophylaxis. Studying the reported cases of <it>P. vivax </it>malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to evaluate the extension of the incubation period and to notice that it may be extended in some cases.</p> <p>Methods</p> <p>Descriptive study of every malaria patients who visited the clinic in the last five years. The mean, standard deviation, median, minimum and maximum of all incubation periods were analysed.</p> <p>Results</p> <p>From the total of 80 patients seen in the clinic during the study time, with confirmed diagnosis of malaria, 49 (63%) were infected with <it>P. vivax</it>. Between those, seven had an estimated incubation period varying from three to 12 months and were returned travellers from Brazilian Amazonian states (6) and Indonesia (1). None of them had taken malarial chemoprophylaxis.</p> <p>Conclusions</p> <p>The authors emphasize that considering malaria as a possible cause of febrile syndrome should be a post-travel routine, independent of the time elapsed after exposure in the transmission area, even in the absence of malaria chemoprophylaxis. They speculate that, since there is no current and detailed information about the biological cycle of human malaria plasmodia's in Brazil, it is possible that new strains are circulating in endemic regions or a change in cycle of preexisting strains is occurring. Considering that a prolonged incubation period may confer advantages on the survival of the parasite, difficulties in malaria control might arise.</p