Trypanocidal activity of Brazilian plants against epimastigote forms from Y and Bolivia strains of Trypanosoma cruzi

Chagas disease is one of the main public health problems in Latin America. Since the available treatments for this disease are not effective in providing cure, the screening of potential antiprotozoal agents is essential, mainly of those obtained from natural sources. This study aimed to provide an evaluation of the trypanocidal activity of 92 ethanol extracts from species belonging to the families Annonaceae, Apiaceae, Cucurbitaceae, Lamiaceae, Lauraceae, Moraceae, Nyctaginaceae, and Verbenaceae against the Y and Bolivia strains of Trypanosoma cruzi. Additionally, cytotoxic activity on LLCMK2 fibroblasts was evaluated. Both the trypanocidal activity and cytotoxicity were evaluated using the MTT method, in the following concentrations: 500, 350, 250, and 100 µg/mL. Benznidazole was used for positive control. The best results among the 92 samples evaluated were obtained with ethanol extracts of Ocotea paranapiacabensis (Am93) and Aegiphila lhotzkiana (Am160). Am93 showed trypanocidal activity against epimastigote forms of the Bolivia strain and was moderately toxic to LLCMK2 cells, its Selectivity Index (SI) being 14.56, while Am160 showed moderate trypanocidal activity against the Bolivia strain and moderate toxicicity, its SI being equal to 1.15. The screening of Brazilian plants has indicated the potential effect of ethanol extracts obtained from Ocotea paranapiacabensis and Aegiphila lhotzkiana against Chagas disease.

Putting prey and predator into the CO2 equation-qualitative and quantitative effects of ocean acidification on predator-prey interactions

Little is known about the impact of ocean acidification on predator-prey dynamics. Herein, we examined the effect of carbon dioxide (CO(2)) on both prey and predator by letting one predatory reef fish interact for 24 h with eight small or large juvenile damselfishes from four congeneric species. Both prey and predator were exposed to control or elevated levels of CO(2). Mortality rate and predator selectivity were compared across CO(2) treatments, prey size and species. Small juveniles of all species sustained greater mortality at high CO(2) levels, while large recruits were not affected. For large prey, the pattern of prey selectivity by predators was reversed under elevated CO(2). Our results demonstrate both quantitative and qualitative consumptive effects of CO(2) on small and larger damselfish recruits respectively, resulting from CO(2)-induced behavioural changes likely mediated by impaired neurological function. This study highlights the complexity of predicting the effects of climate change on coral reef ecosystems.

Desenvolvimento de uma plataforma modelo para a busca de ligantes com potencial leishmanicida baseado na inibição seletiva da enzima diidroorotato desidrogenase

As doenças tropicais negligenciadas (DTNs) causam um imenso sofrimento para a pessoa acometida e em muitos casos podem levar o indivíduo a morte. Elas representam um obstáculo devastador para a saúde e continuam a ser um sério impedimento para a redução da pobreza e desenvolvimento socioeconômico. Das 17 doenças desse grupo, a leishmaniose, incluindo a leishmaniose cutânea, tem grande destaque devido sua alta incidência, os gastos para o tratamento e as complicações geradas em processos de coinfecção. Ainda mais agravante, os investimentos direcionados ao controle, combate e principalmente a inovação em novos produtos é ainda muito limitado. Atualmente, a academia tem um importante papel na luta contra essas doenças através da busca de novos alvos terapêuticos e também de novas moléculas com potencial terapêutico. É nesse contexto que esse projeto teve como meta a implantação de uma plataforma para a identificação de moléculas com atividade leishmanicida. Como alvo terapêutico, optamos pela utilização da enzima diidroorotato desidrogenase de Leishmania Viannia braziliensis (LbDHODH), enzima de extrema importância na síntese de novo de nucleotídeos de pirimidina, cuja principal função é converter o diidroorotato em orotato. Esta enzima foi clonada, expressa e purificada com sucesso em nosso laboratório. Os estudos permitiram que a enzima fosse caracterizada cineticamente e estruturalmente via cristalografia de raios- X. Os primeiros ensaios inibitórios foram realizados com o orotato, produto da catálise e inibidor natural da enzima. O potencial inibitório do orotato foi mensurado através da estimativa do IC50 e a interação proteína-ligante foi caracterizada através de estudos cristalográficos. Estratégias in silico e in vitro foram utilizadas na busca de ligantes, através das quais foram identificados inibidores para a enzima LbDHODH. Ensaios de validação cruzada, utilizando a enzima homóloga humana, permitiram identificar os ligantes com maior índice de seletividade que tiveram seu potencial leishmanicida avaliado in vitro contra as formas promastigota e amastigota de Leishmania braziliensis. A realização do presente projeto permitiu a identificação de uma classe de ligantes que apresentam atividade seletiva contra LbDHODH e que será utilizada no planejamento de futuras gerações de moléculas com atividade terapêutica para o tratamento da leishmaniose. Além disso, a plataforma de ensaios otimizada permitirá a avaliação de novos grupos de moléculas como uma importante estratégia na busca por novos tratamentos contra a leishmaniose

Antichagásicos potenciais: síntese e modelagem molecular de híbridos de hidrazonas e liberadores de óxido nítrico

A doença de Chagas é uma parasitose extremamente negligenciada, cujo agente etiológico é o protozoário Trypanosoma cruzi. Atualmente, 21 países da América Latina são considerados regiões endêmicas, onde 75-90 milhões de pessoas estão expostas à infecção, 6-7 milhões estão infectadas e mais de 41 mil novos casos surgem por ano. Entretanto, apenas os fármacos nifurtimox e benznidazol estão disponíveis no mercado. Estes, além da baixa eficácia na fase crônica da parasitose, apresentam diversos efeitos adversos, sendo que no Brasil apenas o benznidazol é utilizado. Este fato mostra a importância de se ampliar o número de fármacos disponíveis e propor quimioterapia mais eficaz para o tratamento da doença de Chagas. Como forma de contribuir para essa busca, este trabalho objetiva a síntese de compostos híbridos bioisostéricos N-acilidrazônicos e sulfonilidrazônicos, contendo grupo liberador de óxido nítrico, com potencial de interação com cisteíno-proteases parasitárias, tais como a cruzaína. Nestes derivados, os grupos liberadores de óxido nítrico utilizados foram os grupos furoxano (contendo substituinte metílico e fenílico) e éster nitrato. Propôs-se a variação de anéis aromáticos substituídos e não-substituídos, com o intuito de avaliar a possível relação estrutura-atividade (REA) desses análogos. Até o momento, somente os compostos da série N-acilidrazônica tiveram avaliação biológica realizada. Os valores de IC50 dos compostos na forma amastigota do parasita variaram entre >100 a 2,88 µM, sendo este último valor comparável ao fármaco de referência. A atividade inibitória frente à cruzaína foi de 25,2 µM a 2,2 µM. Já a liberação de óxido nítrico foi avaliada pelo método indireto de detecção de nitrato e os valores variaram entre 52,0 µM e 4.232,0 µM. Estes são bem inferiores ao composto padrão, além de não se identificar correlação direta entre a atividade biológica e a liberação de NO. Na sequência, os dois compostos mais ativos (6 e 14) foram submetidos a estudos de permeabilidade e de citotoxicidade. O composto 6 foi considerado o de maior permeabilidade segundo o Sistema de Classificação Biofarmacêutica (SCB) e todos os compostos apresentaram a taxa de fluxo menor que 2, indicando a ausência de mecanismo de efluxo. Na avaliação do potencial citotóxico desses compostos em células humanas, o derivado 6 apresentou índice de seletividade superior ao do benznidazol. Em estudos de modelagem molecular usando análise exploratória de dados (HCA e PCA), propriedades estéricas/geométricas e eletrônicas foram consideradas as mais relevantes para a atividade biológica. Além disso, estudos de docking mostraram que a posição do grupo nitro no anel aromático é importante para a interação com a cruzaína. Ademais o composto 6 não provocou mudanças significativas no ciclo celular e na fragmentação de DNA em células humanas, mostrando-se como líder promissor para futuros estudos in vivo. Atividade tripanomicida, citotoxicidade, potencial de liberação de NO e estudos de permeabilidade dos 23 derivados sulfonilidrazônicos e ésteres nitrato estão sendo avaliados.

Ocean acidification affects the phyto-zoo plankton trophic transfer efficiency

The critical role played by copepods in ocean ecology and biogeochemistry warrants an understanding of how these animals may respond to ocean acidification (OA). Whilst an appreciation of the potential direct effects of OA, due to elevated pCO2, on copepods is improving, little is known about the indirect impacts acting via bottom-up(food quality) effects. We assessed, for the first time, the chronic effects of direct and/or indirect exposures to elevated pCO2 on the behaviour, vital rates, chemical and biochemical stoichiometry of the calanoid copepod Acartia tonsa. Bottom-up effects of elevated pCO2 caused species-specific biochemical changes to the phytoplanktonic feed, which adversely affected copepod population structure and decreased recruitment by 30 %. The direct impact of elevated pCO2 caused gender-specific respiratory responses in A.tonsa adults, stimulating an enhanced respiration rate in males (> 2-fold), and a suppressed respiratory response in females when coupled with indirect elevated pCO2 exposures. Under the combined indirect+direct exposure, carbon trophic transfer efficiency from phytoplankton-to-zooplankton declined to < 50 % of control populations, with a commensurate decrease in recruitment. For the first time an explicit role was demonstrated for biochemical stoichiometry in shaping copepod trophic dynamics. The altered biochemical composition of the CO2-exposed prey affected the biochemical stoichiometry of the copepods, which could have ramifications for production of higher tropic levels, notably fisheries. Our work indicates that the control of phytoplankton and the support of higher trophic levels involving copepods have clear potential to be adversely affected under future OA scenarios.

In vitro anti-canine distemper virus activity of fucoidan extracted from the brown alga Cladosiphon okamuranus

Canine distemper virus (CDV) is a morbillivirus related to measles virus that infects dogs and other carnivores. CDV has a significant global impact on animal health; however, there is no current antiviral treatment for CDV infection. In recent years, it has been demonstrated that sulfated polysaccharides exhibit antiviral properties both in vivo and in vitro, despite their low cytotoxicity to host cells. Fucoidan is a sulfated polysaccharide found in the cell wall matrix of brown algae. In this study, we evaluated in vitro anti-CDV activity of fucoidan, which was derived from Cladosiphon okamuranus. Fucoidan actively inhibited CDV replication in Vero cells at a 50% inhibitory concentration (IC50) of 0.1 lg/ml. The derived selectivity index (SI50) was[20,000. This polysaccharide likely inhibits viral infection by interference in the early steps and by inhibiting CDV-mediated cell fusion. Fucoidan may be useful in development of pharmacological strategies to treat and control CDV infection.

Influence of disaccharide structure on prebiotic selectivity in vitro

To obtain structure-function information of a range of carbohydrates, which are available only in very small quantities, an in vitro fermentation method using 7 mg of carbohydrate, 0.7 mL of basal medium, and 1% (w/v) of fecal bacteria was validated against a pH-controlled batch culture with 150 mL of basal medium and 1.5g of test carbohydrate. This method was used to determine the influence of different glycosidic linkages and monosaccharide compositions of disaccharides on the selectivity of microbial fermentation. A prebiotic index (PI) was calculated for each disaccharide. Generally, disaccharides with linkages of 1-2, 1-4, and 1-6 generated a high PI score, with kojibiose and sophorose showing the greatest values (21.62 and 18.63, respectively). Apart from 6 alpha-mannobiose, mannose-containing disaccharicles gave a low PI due to low numbers of bifidobacteria and lactobacilli and an increase in bacteroides. The structure-function information obtained in this study may lead to a predictive understanding of how specific structures are fermented by the human gut microflora.

Beta-blocker selectivity and airways obstruction

In this Drug Points article the author describes a case of unrecognised airways disease where prescribing timolol resulted in shortness of breath and comments on the issues it raises.

Thinking about a limited future enhances the positivity of younger and older adults’ recall: support for socioemotional selectivity theory

Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants’ recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults’ recall is typically more positive than younger adults’ recall may index naturally shifting time horizons and goals with age.

A further exploration of a nucleophilicity index based on the gas-phase ionization potentials

An empirical nucleophilicity index based on the gas-phase ionization potentials has been recently shown to be useful categorizing and settling the nucleophilicity power of a series of captodative ethylenes reacting in cycloaddition reactions (L.R. Domingo, E. Chamorro, P. Perez, Journal of Organic Chemistry 73 (2008) 4615-4624). In the present work, the applicability of such model is tested within a broader series of substituted alkenes, substituted aromatic compounds and simple nucleophilic molecules. This index obtained within a Koopman`s theorem framework has been evaluated here in both gas and solution phases for several well-known nucleophiles. These results are found to be linearly correlated. Finally, the feasibility of the predictive character of this index has been discussed in comparison to the available experimental nucleophilicities of some amines in water. These results further support and validate the usefulness of such approximation in the modeling of the global nucleophilicity. (C) 2008 Elsevier B.V. All rights reserved.

Feeding selectivity of ichthyofauna in a tropical stream: space-time variations in trophic plasticity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The SB-index and the HSB-index: efficient indices for spatial data warehouses

Spatial data warehouses (SDWs) allow for spatial analysis together with analytical multidimensional queries over huge volumes of data. The challenge is to retrieve data related to ad hoc spatial query windows according to spatial predicates, avoiding the high cost of joining large tables. Therefore, mechanisms to provide efficient query processing over SDWs are essential. In this paper, we propose two efficient indices for SDW: the SB-index and the HSB-index. The proposed indices share the following characteristics. They enable multidimensional queries with spatial predicate for SDW and also support predefined spatial hierarchies. Furthermore, they compute the spatial predicate and transform it into a conventional one, which can be evaluated together with other conventional predicates by accessing a star-join Bitmap index. While the SB-index has a sequential data structure, the HSB-index uses a hierarchical data structure to enable spatial objects clustering and a specialized buffer-pool to decrease the number of disk accesses. The advantages of the SB-index and the HSB-index over the DBMS resources for SDW indexing (i.e. star-join computation and materialized views) were investigated through performance tests, which issued roll-up operations extended with containment and intersection range queries. The performance results showed that improvements ranged from 68% up to 99% over both the star-join computation and the materialized view. Furthermore, the proposed indices proved to be very compact, adding only less than 1% to the storage requirements. Therefore, both the SB-index and the HSB-index are excellent choices for SDW indexing. Choosing between the SB-index and the HSB-index mainly depends on the query selectivity of spatial predicates. While low query selectivity benefits the HSB-index, the SB-index provides better performance for higher query selectivity.

Association Between Parity, Pre-pregnancy Body Mass Index And Gestational Weight Gain.

To analyze the relationship between parity, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG). This observational controlled study was conducted from November 2013 to April 2014, with postpartum women who started antenatal care up to 14 weeks and had full-term births. Data were collected from medical records and antenatal cards. Descriptive and bivariate analyses were performed. The significance level was 5%. Data were collected from 130 primiparous and 160 multiparous women. At the beginning of prenatal care, 54.62% of the primiparous were eutrophic, while the majority of multiparous were overweight or obese (62.51%). Multiparas are two times more likely to be obese at the beginning of their pregnancies, when compared to primiparas. The average pre-pregnancy weight and final pregnancy weight was significantly higher in multiparous, however, the mean GWG was higher among primiparous. We found an inverse correlation between parity and the total GWG, but initial BMI was significantly higher in multiparas. Nevertheless, monitoring of the GWG through actions that promote a healthier lifestyle is needed, regardless of parity and nutritional status, in order to prevent excessive GWG and postpartum weight retention and consequently inadequate pre-pregnancy nutritional status in future pregnancies.

Sorghum Flour Fractions: Correlations Among Polysaccharides, Phenolic Compounds, Antioxidant Activity And Glycemic Index.

Nutrients composition, phenolic compounds, antioxidant activity and estimated glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF). Correlation between EGI and the studied parameters were determined. SB presented the highest protein, lipid, ash, β-glucan, total and insoluble dietary fiber contents; and the lowest non-resistant and total starch contents. The highest carbohydrate and resistant starch contents were in DSF and WSF, respectively. Phenolic compounds and antioxidant activities were concentrated in SB. The EGI values were: DSF 84.5±0.41; WSF 77.2±0.33; and SB 60.3±0.78. Phenolic compounds, specific flavonoids and antioxidant activities, as well as total, insoluble and soluble dietary fiber and β-glucans of sorghum flour samples were all negatively correlated to EGI. RS content was not correlated to EGI.

Validação da Body Appreciation Scale (BAS), Life Satisfaction Index for the Third Age (LSITA) e do Aging Perception Questionnaire (APQ) para a língua portuguesa no Brasil : um estudo em idosos brasileiros

Universidade Estadual de Campinas . Faculdade de Educação Física