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Viruses are associated with several human diseases that infect a large number of individuals, hence directly affecting global health and economy. Owing to the lack of efficient vaccines, antiviral therapy and emerging resistance strains, many viruses are considered as a potential threat to public health. Therefore, researches have been developed to identify new drug candidates for future treatments. Among them, antiviral research based on natural molecules is a promising approach. Phospholipases A2 (PLA2s) isolated from snake venom have shown significant antiviral activity against some viruses such as Dengue virus, Human Immunodeficiency virus, Hepatitis C virus and Yellow fever virus, and have emerged as an attractive alternative strategy for the development of novel antiviral therapy. Thus, this review provides an overview of remarkable findings involving PLA2s from snake venom that possess antiviral activity, and discusses the mechanisms of action mediated by PLA2s against different stages of virus replication cycle. Additionally, molecular docking simulations were performed by interacting between phospholipids from Dengue virus envelope and PLA2s from Bothrops asper snake venom. Studies on snake venom PLA2s highlight the potential use of these proteins for the development of broad-spectrum antiviral drugs.

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Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50=2.3µM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3(∗)43 (EC50=4.0µM), 3(∗)20 (EC50=8.2µM) and 5(∗)362 (EC50=38.9µM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds.

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In this study ready-to-eat food samples were collected in the production line of the university restaurant of the University of Brasilia, Brazil, which serves non-vegetarian and vegetarian meals daily. Samples were analysed for the presence of ten organophosphorus insecticides (OPs) by GC/FPD, after extraction with ethyl acetate and anhydrous sodium sulfate (LOQ = 0.002 mg kg(-1)), and for dithiocarbamate fungicides, as CS(2), using the spectrophotometric method (LOQ = 0.05 mg kg(-1)). About 43% of the 175 samples analysed contained at least one OP compound at levels up to 1.83 mg kg(-1). Methamidophos was the compound most detected (37.7%), present in most of the soup, soybean and salad samples. No OP residues were found in fruit juice, beans and bran rice samples. The cumulative acute intake of OPs was estimated using methamidophos and acephate as index compounds (IC). The total cumulative intake represented 9.1% and 47.7% of the methamidophos ARfD for the non-vegetarian and vegetarian diets, respectively. When acephate was used as IC, the total intakes represented 20.7% and 116% of the ARfD for the non-vegetarian and vegetarian diets, respectively. Dithiocarbamates were detected in 70% of the 177 samples analysed, at levels up to 0.51 mg kg(-1) CS(2); all salad samples were positive and no residues were found in fruit juice. The chronic intake of dithiocarbamates represented 8.6 and 8.9% of the ADI (mancozeb) for the vegetarian and non vegetarian diets, respectively.

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Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-α and ribavirin therapy. Major histocompatibility complex class I restricted CD8(+) T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated α-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy.

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Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responsesand the combination of pegylated interferon (INF)-a and ribavirin therapy. Major histocompatibility complex class Irestricted CD8+ T cells are responsible for the control of viraemia in HCV infection, and several studies suggestprotection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated a-INF with ribavirin therapy and test evidence of natural.

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The results obtained through biological research usually need to be analyzed using computational tools, since manual analysis becomes unfeasible due to the complexity and size of these results. For instance, the study of quasispecies frequently demands the analysis of several, very lengthy sequences of nucleotides and amino acids. Therefore, bioinformatics tools for the study of quasispecies are constantly being developed due to different problems found by biologists. In the present study, we address the development of a software tool for the evaluation of population diversity in quasispecies. Special attention is paid to the localization of genome regions prone to changes, as well as of possible hot spots.

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Although there have been advances in methods for extracting information about dispersal processes, it is still very difficult to measure them. Predicting dispersal groups using single readily-measured traits would facilitate the emergence of instructive comparisons among ecological strategies of plants and offer a path towards improved synthesis across field experiments. The leaf-height-seed scheme consists of three functional traits: specific leaf area, plant canopy height, and seed mass. We tested, applying logistic regression analysis, whether these traits are potential predictors of dispersal guilds in a disjoint cerrado woodland site in southeastern Brazil. According to our results, none of the plant traits studied could predict dispersal guild; this means that abiotically and biotically dispersed species showed similar values of specific leaf area, height, and seed mass. The species of both guilds exhibited sclerophylly, probably a result of the typical soil nutrient deficiency of cerrado, which also may have placed constraints upon plant canopy height regardless of the dispersal mode. In the cerrado, some abiotically dispersed trees might present higher than expected seed mass as support to the investment in high root-to-shoot ratio at the seedling stage. Seeds of bird-dispersed species are limited in size and mass because of the small size of most frugivorous birds. Since soil nutrient quality might contribute to the similarity between the dispersal guilds regarding the three traits of the scheme, other plant traits (e.g., root depth distribution and nutrient uptake strategy) that detail the former should be considered in future predictive studies.

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Although there have been advances in methods for extracting information about dispersal processes, it is still very difficult to measure them. Predicting dispersal groups using single readily-measured traits would facilitate the emergence of instructive comparisons among ecological strategies of plants and offer a path towards improved synthesis across field experiments. The leaf-height-seed scheme consists of three functional traits: specific leaf area, plant canopy height, and seed mass. We tested, applying logistic regression analysis, whether these traits are potential predictors of dispersal guilds in a disjoint cerrado woodland site in southeastern Brazil. According to our results, none of the plant traits studied could predict dispersal guild; this means that abiotically and biotically dispersed species showed similar values of specific leaf area, height, and seed mass. The species of both guilds exhibited sclerophylly, probably a result of the typical soil nutrient deficiency of cerrado, which also may have placed constraints upon plant canopy height regardless of the dispersal mode. In the cerrado, some abiotically dispersed trees might present higher than expected seed mass as support to the investment in high root-to-shoot ratio at the seedling stage. Seeds of bird-dispersed species are limited in size and mass because of the small size of most frugivorous birds. Since soil nutrient quality might contribute to the similarity between the dispersal guilds regarding the three traits of the scheme, other plant traits (e.g., root depth distribution and nutrient uptake strategy) that detail the former should be considered in future predictive studies.

Embora tenham ocorrido avanços nos métodos de aquisição de informações sobre os processos de dispersão, ainda é difícil medi-los. Predizer grupos de dispersão usando atributos simples e práticos facilitaria o aparecimento de comparações instrutivas entre as estratégias ecológicas das plantas e ofereceria um caminho em direção à síntese efetiva de experimentos de campo. O esquema Folha-Altura-Semente consiste em três atributos funcionais: área foliar específica, altura e massa da semente. Testamos, aplicando análise de regressão logística, se esses atributos são potenciais previsores das guildas de dispersão em uma área disjunta de cerrado sensu stricto no Sudeste brasileiro. Segundo os nossos resultados, nenhum dos atributos estudados pôde prever a guilda de dispersão. Isso significa que espécies abiótica e bioticamente dispersas apresentaram valores similares de área foliar específica, altura e massa da semente. As espécies de ambas as guildas exibiram esclerofilia, provavelmente um resultado da deficiência nutricional típica dos solos do cerrado, o que, por sua vez, pode ter limitado à altura das espécies independentemente do seu modo de dispersão. No cerrado, algumas árvores com dispersão abiótica podem apresentar sementes mais pesadas do que o esperado devido ao investimento em elevada razão raiz-caule no estádio de plântula. Sementes de espécies ornitocóricas são limitadas no seu tamanho e massa por causa do reduzido tamanho da maioria das aves frugívoras. Uma vez que a qualidade nutricional do solo do cerrado pode contribuir com a similaridade entre as guildas de dispersão no que diz respeito aos três atributos do esquema, outros atributos (por ex., distribuição da profundidade da raiz e estratégia de captação de nutrientes) que detalhem a primeira devem ser considerados em estudos futuros.

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Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29% for the C282Y mutation, 13.72, 13.70, and 9.54% for the H63D mutation, and 0, 0.60, and 0.87% for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

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Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29 percent for the C282Y mutation, 13.72, 13.70, and 9.54 percent for the H63D mutation, and 0, 0.60, and 0.87 percent for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

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AIM: To evaluate the use of local transdermic anesthetics in fine needle aspiration biopsy (FNAB) in breast lesions. METHODS: Prospective randomized study of 119 patients having breast lesions, all being indicated for FNAB. The patients were divided into three groups: 40 patients entered in the active group (lidocaine + prilocaine); 40 patients underwent the placebo group (aqueous extract of Triticum vulgaris); and a control group of 39 women in whom FNAB was performed without the administration of any substance. Both the anesthetic and placebo were administered an hour before FNAB. Pain was quantified through a visual analogic scale of pain. The type of pain was also classified in terms of occurrence: only during the puncture, only during the movements and both. RESULTS: The visual linear analogic scale of pain showed an average of 3.3 in the active group, 3.5 in the placebo and 4.0 in the control group (NS). Analysis of the type of pain which was referred by the patient showed that 15% of the patients in the active group, 12.5% of those in the placebo group and 5.1% in the control group did not refer to any sensation of pain. Pain, when felt, was similar in all three groups (p < 0.4). CONCLUSIONS: Both the quantification and the type of pain referred to were similar in all three groups. However, there was a tendency of the patient to refer to less pain when the active substance or the placebo were used, when results were compared to the control group.

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Peripheral blood mononuclear cells (PBMC) from 13 American tegumentary leishmaniasis (ATL) patients and two healthy controls were tested in in vitro proliferative response assays with crude lipophosphoglycan (LPG), purified LPG, LPG-associated proteins (LPGAP) and synthetic LPGAP from L. donovani. Cells from another group of six ATL patients were similarly tested with LPGAP obtained from L. major. L. major LPGAP was more stimulatory than L. donovani LPGAP. Crude LPG from L. donovani was significantly more stimulatory than all the other L. donovani antigens tested, including L. donovani LPGAP. The present results indicate that the association with the glycolipid (LPG) may enhance the antigenicity of LPGAP for human T lymphocytes.

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Num estudo retrospectivo de 259 mortes perinatais ocorridas nas duas maternidades centrais de Coimbra, Portugal entre janeiro de 1985 a julho de 1987, procurou-se classificar as causas de acordo com o metodo sugerido por Wigglesworth. Asfixia foi causa primaria em 21,6%, sendo 30 de 259 em bebes com mais de 2500 gramas. Quinze por cento foram causas por malformacoes letais, 26% estavam associadas a imaturidade e 27,7% eram natimortos macerados. Apesar de necropsia estar faltando em 2/3 dos casos, acreditamos que a classificacao pode ser utilizada onde esta facilidade nao e sempre disponivel. Problemas na alocacao para diferentes grupos de causas sao discutidos, assim com sugestoes para facilitar o uso da classificacao onde exames post-mortem sao dificeis ou impossiveis de obter .

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This paper "describes the demographic occupation of the national territory [of Brazil] between 1960 and 1980, taking into account four areas according to their population and area: totally occupied, suboccupied, partially occupied and unoccupied. For each occupied area it describes [the] main economic and demographic features and observes the population redistribution [that] occurred in Brazil during that period." (SUMMARY IN ENG)

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