DETC Induces Leishmania Parasite Killing in Human In Vitro and Murine In Vivo Models: A Promising Therapeutic Alternative in Leishmaniasis

Background: Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings: We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p,0.001) and is able to ??????sterilize?????? Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p,0.001) and parasite destruction (p,0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p,0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection

Reduction of volatile acidity of wines by selected yeast strains

Herein we isolate and characterize wine yeasts with ability to reduce volatile acidity of wines using a refermentation process, which consists in mixing the acidic wine with freshly crushed grapes or musts or, alternatively, in the incubation with the residual marc. From a set of 135 yeast isolates, four strains revealed ability to use glucose and acetic acid simultaneously. Three of them were identified as Saccharomyces cerevisiae and one as Lachancea thermotolerans. Among nine commercial S. cerevisiae strains, strains S26, S29 and S30 display similar glucose and acetic acid initial simultaneous consumption pattern and were assessed in refermentation assays. In a medium containing an acidic wine with high glucose/low ethanol concentrations, under low oxygen availability, strain S29 is the most efficient one, whereas L. thermotolerans 44C is able to decrease significantly acetic acid similar to the control strain Zygosaccharomyces bailii ISA 1307, but only under aerobic conditions. Conversely, for low glucose/high ethanol concentrations, under aerobic conditions, S26 is the most efficient acid degrading strain, while under limited-aerobic conditions, all the S. cerevisiae strains studied display acetic acid degradation efficiencies identical to Z. bailii. Moreover, S26 strain also reveals capacity to decrease volatile acidity of wines. Together, the S. cerevisiae strains characterized herein appear promising for the oenological removal of volatile acidity of acidic wines.Fundação para a Ciência e a Tecnologia (FCT) - Programa POCI 2010 (FEDER/FCT, POCI/AGR/56102/2004, PTDC/AGRALI/71460/2006

The fate of acetic acid during glucose co-metabolism by the spoilage yeast Zygosaccharomyces bailii

Zygosaccharomyces bailii is one of the most widely represented spoilage yeast species, being able to metabolise acetic acid in the presence of glucose. To clarify whether simultaneous utilisation of the two substrates affects growth efficiency, we examined growth in single- and mixed-substrate cultures with glucose and acetic acid. Our findings indicate that the biomass yield in the first phase of growth is the result of the weighted sum of the respective biomass yields on single-substrate medium, supporting the conclusion that biomass yield on each substrate is not affected by the presence of the other at pH 3.0 and 5.0, at least for the substrate concentrations examined. In vivo(13)C-NMR spectroscopy studies showed that the gluconeogenic pathway is not operational and that [2-(13)C]acetate is metabolised via the Krebs cycle leading to the production of glutamate labelled on C(2), C(3) and C(4). The incorporation of [U-(14)C]acetate in the cellular constituents resulted mainly in the labelling of the protein and lipid pools 51.5% and 31.5%, respectively. Overall, our data establish that glucose is metabolised primarily through the glycolytic pathway, and acetic acid is used as an additional source of acetyl-CoA both for lipid synthesis and the Krebs cycle. This study provides useful clues for the design of new strategies aimed at overcoming yeast spoilage in acidic, sugar-containing food environments. Moreover, the elucidation of the molecular basis underlying the resistance phenotype of Z. bailii to acetic acid will have a potential impact on the improvement of the performance of S. cerevisiae industrial strains often exposed to acetic acid stress conditions, such as in wine and bioethanol production.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal Grant PTDC/AGR-ALI/102608/2008 and by project FCOMP-01-0124-FEDER- 007047 and by FEDER through POFC - COMPETE and national funds from FCT - project PEst-C/BIA/UI4050/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Relationship arachidonic acid (ARA): docosahexaenoic acid (DHA) in the body composition of Nile tilapia fed with diets containing the microalgae Schizochytrium sp.

Todos os textos, informa??es e resultados apresentados s?o de inteira responsabilidade dos autores.Ag?ncias financiadoras para a realiza??o do trabalho: Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq), Alltech Inc., Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) e Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG).O ?cido araquid?nico compete com DHA pelas mesmas vias metab?licas na forma??o de membranas e constitui??o das c?lulas do f?gado. Isto sugere que a ingest?o de DHA podem substituir parcialmente o ?cido araquid?nico atrav?s da modifica??o da composi??o de ?cidos graxos nos tecidos, o que reduz a ocorr?ncia de desordens nos sitema imune e doen?as inflamat?rias. Com isso, objetivou-se avaliar a rela??o ARA : DHA corporal de alevinos de til?pia do Nilo alimentadas com ra??es contendo a microalga Schizochytrium sp..Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG)The arachidonic acid competes with DHA by the same pathways in the formation of membranes and formation of liver cells. This suggests that intake of DHA may partially replace arachidonic acid by modifying the composition of fatty acids in tissues, reducing the occurrence of immune system disorders and inflammatory diseases. The relationship ARA: DHA body of Nile tilapia fry fed diets containing the microalgae Schizochytrium sp. was evaluated

Microalgae Schizochytrium sp. in diets for Piau juvenilles

Todos os textos, informa??es e resultados apresentados s?o de inteira responsabilidade dos autores.O DHA ? um ?cido importante da s?rie ?mega 3, fundamental para a forma??o do tecido nervoso e visual em humanos, e confere tamb?m uma boa forma??o da massa encef?lica. O presente trabalho teve o objetivo de avaliar dietas contendo a inclus?o da alga Schizochytrium sp. no desempenho produtivo de juvenis de piau.O experimento foi conduzido no Laborat?rio de Aquicultura e Ecologia Aqu?tica do Departamento de Zootecnia da Universidade Federal dos Vales do Jequitinhonha e Mucuri, em Diamantina MG. Foram utilizados 300 juvenis de Piau (Leporinus friderici) com peso e comprimento total m?dio de 11,8 e 9,68 g respectivamente . Os peixes passaram por sete dias de adapta??o e foram alimentados com a ra??o do tratamento controle. . O experimento foi realizado em um delineamento inteiramente casualizado, com cinco tratamentos (0, 10, 20, 30, e 40 g de Schizochytrium sp/kg-1)e quatro repeti??es. Sete juvenis foram estocados por aqu?rio, totalizando 20 parcelas experimentais. Avaliou-se aos 60 dias de experimento par?metros de desempenho produtivo. Foram mensurados: comprimento padr?o (cm), comprimento total (cm), ganho de peso (g), consumo de ra??o (g), convers?o alimentar (g/g)?, biomassa final (g), e sobreviv?ncia (%). As vari?veis de desempenho apresentaram melhores resultados de acordo com o aumento do n?vel de inclus?o da alga Schizochytrium sp em juvenis de piau. Conlcui-se com este estudo que juvenis de piau alimentados com 40g de Schizochytrium sp.kg-1 apresentam melhor desempenho produtivo e sobreviv?ncia.DHA is an important acid of the omega-3 series, essential for the formation of the nervous and visual tissue in humans, and also gives a good formation of brain matter. This study aimed to evaluate diets with the inclusion of algae Schizochytrium sp. In productive performance of piau juveniles.. Experiment was conducted at the Aquaculture Laboratory of Aquatic Ecology of the Department of Animal Science, of the Federal University of the Jequitinhonha and Mucuri Valleys, in Diamantina MG. . Three hundred Piau (Leporinus friderici) juvenile, with body weight and length means of 11.8, and 9.68 g respectively. Fish have undergone seven days of adaptation and were fed with the control ration treatment. The experiment was conducted in a completely randomized design, with five treatments (0, 10, 20, 30, and 40 g of Schizochytrium sp. Kg-1) and four replications. Seven juveniles were stocked per aquarium, totaling 20 experimental plots. It was evaluated at 60 days of the experiment For the productive performance were measured: standard length (cm), total length (cm), weight gain (g), feed intake (g), feed conversion (g / g) ? , final biomass (g) EC (%) and survival (%). The performance variables showed greater results in accordance with the increase in the level of inclusionof Schizochytrium sp in piau juveniles diets. It follows that piau juveniles fed with 40g Schizochytrium sp.kg-1 have greater growth performance and survival