Adenosine and Immune Imbalance in Visceral Leishmaniasis: The Possible Role of Ectonucleotidases

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is responsible for most Leishmania-associated deaths. VL represents a serious public health problem that affects many countries. The immune response in leishmaniasis is very complex and is poorly understood. The Th1 versus Th2 paradigm does not appear to be so clear in visceral leishmaniasis, suggesting that other immunosuppressive or immune-evasion mechanisms contribute to the pathogenesis of VL. It has been demonstrated that generation of adenosine, a potent endogenous immunosuppressant, by extracellular enzymes capable to hydrolyze adenosine tri-nucleotide (ATP) at the site of infection, can lead to immune impairment and contribute to leishmaniasis progression. In this regard, this paper discusses the unique features in VL immunopathogenesis, including a possible role for ectonucleotidases in leishmaniasis

Phosphatase activity characterization on the surface of intact bloodstream forms of Trypanosoma brucei

Procyclic forms of Trypanosoma brucei possess a phosphatase activity on their external cell surface. This activity, while it dephosphorylates [P-32]phosphocasein, is inhibited weakly by NaF and tartrate but strongly by vanadate. in this work, we describe the presence of an external phosphatase activity in intact bloodstream forms of T brucei. With p-nitrophenyl phosphate (pNPP) as substrate, these intact cells produced 3-5 nmol pNP min(-1) mg(-1), linearly for up to at least 30 min. the activity was not significantly increased by Mg2+, Mn2+, Ca2+ and Co2+, but was inhibited by vanadate, NaF, p-chloromercuribenzoate and Zn2+ and was insensitive to okadaic acid. Membrane-enriched fractions of parasites contained an acid phosphatase activity, with a pH optimum in the range of 4.5-5.5. This activity hydrolyzed phosphotyrosine (40 nmol phosphate min(-1) mg(-1)) better than phosphothreonine or phosphoserine. Partial purification of this phosphatase yielded a single activity band following gel electrophoresis, a K-m value of 0.29 mM with pNPP and was insensitive to the Fe2+/H2O2/ascorbate system. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.Universidade Federal de São Paulo, Dept Bioquim, BR-04023900 Sao Carlos, SP, BrazilUniv São Paulo, Fac Odontol, Dept Ciencias Biol, Bauru, SP, BrazilUniv Fed Rio de Janeiro, Inst Ciencias Biol, Dept Bioquim, Rio de Janeiro, RJ, BrazilUniv Estadual Campinas, Inst Biol, Dept Bioquim, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Bioquim, BR-04023900 Sao Carlos, SP, BrazilWeb of Scienc

Inorganic Phosphate as an Important Regulator of Phosphatases

Cellular metabolism depends on the appropriate concentration of intracellular inorganic phosphate (Pi). Pi starvation-responsive genes appear to be involved in multiple metabolic pathways, implying a complex Pi regulation system in microorganisms and plants. A group of enzymes is required for absorption and maintenance of adequate phosphate levels, which is released from phosphate esters and anhydrides. The phosphatase system is particularly suited for the study of regulatory mechanisms because phosphatase activity is easily measured using specific methods and the difference between the repressed and derepressed levels of phosphatase activity is easily detected. This paper analyzes the protein phosphatase system induced during phosphate starvation in different organisms

Leishmania amazonensis: Inhibition of 3′-nucleotidase activity by Cu2+ ions

AbstractFree Cu2+ is toxic due to the capacity of free copper ions to catalyze the production of reactive oxygen species (ROS) that can modify the structure and/or function of biomolecules. In addition, non-specific binding to enzymes, which modifies their catalytic activities, can occur. In this work, the mechanisms underlying the ability of copper to inhibit 3′-nucleotidase from Leishmania amazonensis (La3′-nucleotidase) were investigated. To that end, La3′-nucleotidase activity was assayed with CuCl2 in the presence of ascorbate or hydrogen peroxide to discriminate non-specific binding effects from pro-oxidant effects of copper. Copper inhibitory effects were greater at more acidic pH than at alkaline pH. The addition of enzyme substrate, adenosine 3′-monophosphate (3′AMP), prevented the inhibition of enzyme activity by copper. Thiol-containing compounds were able to protect the enzyme activity against inhibition due to copper. The specific copper chelating agent bathocuproine sulphonate (BCS) restored enzyme activity after pre-treatment of the enzyme with copper. La3′-nucleotidase activity was found to be resistant to ROS generated during oxidation reactions of ascorbate and hydrogen peroxide catalyzed by copper. Our results suggest that Cu2+ ions exert their inhibitory effects by binding to specific motifs of the 3′-nucleotidase protein and that the enzyme appears to be extremely resistant to ROS

Análisis de factibilidad técnica-económica de la implementación de un producto a base de pomasa de manzana para la industria de cecinas

48 p.La carne constituye actualmente un componente importante en la dieta del mundo occidental. Sin embargo, diversos estudios recomiendan reducir su ingesta debido a su alto contenido calórico, graso y de sodio, debido principalmente a la incorporación de grasa animal y sal dentro de sus productos cárnicos, las que se relacionan con enfermedades cardiovasculares, el cáncer y la obesidad. Últimamente se ha tornado relevante incorporar alimentos saludables en la dieta. La fibra vegetal es un componente, que permite reemplazar un porcentaje de grasa, y otorga cualidades saludables en un embutido cárnico. El objetivo de esta memoria de título es realizar un estudio técnico-económico en la implementación del nuevo producto (chorizo parrillero con inclusiones de fibras de pomasa de manzana) en el mercado de cecinas. Donde los objetivos específicos consistieron en 1) realizar una propuesta de valor, para analizar la demanda potencial asociado al nuevo producto cárnico, y 2) evaluar soluciones técnicas productivas y financiera de la implementación. Para esta evaluación se obtuvo el apoyo de la empresa Agrosuper, quienes facilitaron sus instalaciones e información necesaria para obtener un resultado satisfactorio. En primer lugar, se realizó un análisis del mercado, a través de una encuesta que buscaba conocer la disponibilidad a pagar de los consumidores por este nuevo producto, y segmentar el mercado al cual se quiere llegar. A continuación, se desarrolló un análisis FODA con el que se obtiene un posicionamiento estratégico del producto, con sus cualidades internas y externas con respecto al mercado, luego se desarrolla un plan de marketing con una matriz CANVAS, con el fin de identificar las necesidades del mercado y darle un valor agregado al producto. Finalmente se desarrolla el diagrama de flujo del nuevo producto, para ver las variaciones posibles dentro de su línea de trabajo, y su efecto en el análisis final que correspondió a la evaluación financiera, a través de un flujo de caja diferencial. De acuerdo con el estudio realizado, basándonos en datos reales obtenidos de la empresa Agrosuper, y a través de análisis al mercado, se obtiene que la implementación del producto de innovación en el mercado de cecinas es rentable, ya que los indicadores de rentabilidad (VAN y TIR), están sobre sus parámetros de comparación, es decir, el VAN (valor actual neto) es mayor a cero y la TIR (tasa interna de retorno) es mayor a la tasa de descuento utilizada del 9,50%. Por lo tanto, la incorporación de este nuevo embutido en la línea productiva de cualquier empresa productora de cecinas, le generará riquezas./ABSTRACT: Meat is currently an important component in the diet of the Western world. However, several studies recommend reducing their intake because of their high caloric, fat and sodium content, mainly due to the incorporation of animal fat and salt into their meat products, which are related to cardiovascular diseases, cancer and obesity. Lately it has become relevant to incorporate healthy foods into the diet. Vegetable fiber is a component, which allows replacing a percentage of fat, and gives healthy qualities in a meat sausage. The objective of this title report is to carry out a technicaleconomic study in the implementation of the new product (chorizo broiler with inclusions of fibers of apple pomasa) in the market of cecins. Where the specific objectives consisted of 1) making a value proposition, to analyze the potential demand associated with the new meat product, and 2) evaluating productive and financial technical solutions of the implementation. For this evaluation was obtained the support of the company Agrosuper, who provided their facilities and information necessary to obtain a satisfactory result. In the first place, a market analysis was carried out, through a survey that sought to know the consumers' willingness to pay for this new product, and to segment the market to which it was intended. Next, a SWOT analysis was developed to obtain a strategic positioning of the product, with its internal and external qualities with respect to the market, and then developed a marketing plan with a CANVAS matrix, in order to identify the needs of the Market and give added value to the product. Finally, the flow diagram of the new product is developed, to see the possible variations within its line of work, and its effect in the final analysis that corresponded to the financial evaluation, through a differential cash flow. According to the study, based on real data obtained from the company Agrosuper, and through analysis to the market, it is obtained that the implementation of the innovation product in the cecins market is profitable, since the profitability indicators (VAN and TIR) are above their comparison parameters, the NPV (Net Present Value) is greater than zero and the Internal Rate of Return (IRR) is greater than the discount rate used of 9.50%. Therefore, the incorporation of this new inlay in the production line of any company producing cecins will generate you riches

The GTPase TcRjl of the human pathogen Trypanosoma cruzi is involved in the cell growth and differentiation

AbstractThe protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas Disease, undergoes through a complex life cycle where rounds of cell division and differentiation occur initially in the gut of triatominae vectors and, after transmission, inside of infected cells in vertebrate hosts. Members of the Ras superfamily of GTPases are molecular switches which play pivotal regulatory functions in cell growth and differentiation. We have previously described a novel GTPase in T. cruzi, TcRjl, which belongs to the RJL family of Ras-related GTP binding proteins. Here we show that most of TcRjl protein is found bound to GTP nucleotides and may be locked in this stage. In addition, we show that TcRjl is located close to the kinetoplast, in a region corresponding possibly to flagellar pocket of the parasite and the expression of a dominant-negative TcRjl construct (TcRjlS37N) displays a significative growth phenotype in reduced serum medium. Remarkably, overexpression of TcRjl inhibits differentiation of epimastigotes to trypomastigote forms and promotes the accumulation of intermediate differentiation stages. Our data suggest that TcRjl might play a role in the control of the parasite growth and differentiation

Associação entre esclerose múltipla e alelos hla-drb1* em uma população miscigenada de Salvador, Ba, Brasil

Introdução: a esclerose múltipla é uma doença que afeta preferencialmente o sistema nervoso central de mulheres jovens, causandolhes graus variáveis de incapacidades física e cognitiva. Etiologicamente associa fatores ambientais, biológicos, sócio-econômicos e genéticos, como por exemplo genes do MHC classe II, especialmente os alelos HLA-DRB1*. Objetivo: determinar a frequência dos alelos HLA DRB1* em portadores de esclerose múltipla atendidos no centro de referência do C.H.U.P.E.S, UFBA, no período de outubro de 2014 a abril de 2015 e associá-las a variáveis clínico-demográficas. Metodologia: estudo do tipo caso-controle, aprovado pelo comitê de ética da Faculdade de medicina da Universidade Federal da Bahia (CAAE: 3517134.0.0000.5577), que envolveu uma amostra de conveniência composta por 97 indivíduos, cujos dados clínico-demográficos foram coletados através de questionário desenvolvido para a pesquisa. A genotipagem dos alelos HLA-DRB1* foi realizada através da técnica HLA-DR SSO GenotypingTest. Resultados: a análise quantitativa revelou perfil genotípico do tipo HLA-DRB1*15 (20,5%), em mulheres (83,0%), das raças/etnias negra ou parda (75,0%), com faixa etária entre 30 e 39 anos (28,0%). Houve predomínio da forma clínica surtoremissiva da doença (76,0%), dentre os doentes com idade mais avançada (55,0%), sem permanência de sequela clínica (70,0%) e que usavam algum tipo de Interferon (58,0%). A análise qualitativa indicou maiores frequências, na forma progressiva de esclerose múltipla dos grupos alélicos HLA-DRB1*12 (22,0%), e dos alelos HLA-DRB1*13 (12,6%)e HLA-DRB1*15 (22,0%) naqueles indivíduos com a forma surtoremissiva. Negros e pardos demonstraram maior prevalência do alelo HLA-DRB1*15 (24,0%), enquanto que nos brancos houve maior prevalência do alelo HLA-DRB1*07 (20,0%). Conclusão: forte associação entre as frequências alélicas, esclerose múltipla e as variáveis raça/etnia e forma clínica da doença

Avaliação de parâmetros hematológicos e bioquímicos em cães pós-transfundidos com sangue tipo AEC 1.1 positivo

Introdução: sangue tipificado e compatível são parâmetros importantes para uma transfusão sanguínea segura. Transfusão realizada apenas após a prova de compatibilidade não garante igualdade de tipos sanguíneos entre receptor e doador, devido ao fato da não evidência de aloanticorpos naturais nos cães contra os vários tipos sanguíneos. O tipo AEC (Antígeno Eritrocitário Canino) 1.1, por ser o mais imunogênico, causando sensibilização em animais que não possuam esse tipo, apresenta relevância pós-transfusional. Objetivo: o estudo objetivou avaliar o perfil hematológico e bioquímico dos animais receptores de sangue AEC 1.1 positivo, através de hemograma, dosagem de proteínas plasmáticas totais e dosagens séricas de creatinina e gama-glutamiltransferase, e monitorar a presença de aloanticorpos no período pós-transfusional através da prova de reação cruzada. Metodologia: cães com tipo sanguíneo desconhecido foram submetidos à prova de reação cruzada e, a seguir, transfundidos com sangue AEC 1.1 positivo; prova de reação cruzada e os testes laboratoriais foram avaliados nos dias 7, 14, 21 e 28 pós-transfusão. Resultados: no período avaliado, os animais apresentaram índices normais de leucograma, plaquetas, proteínas plasmáticas totais, creatinina e gama-glutamiltransferase. A média dos valores de eritrogramas estiveram abaixo da normalidade, enquanto as provas de reação cruzada apresentaram valores progressivos a cada semana avaliada, evidenciando presença de aloanticorpos ou autoanticorpos em alguns receptores. Conclusão: os parâmetros hematológicos e bioquímicos avaliados nos animais pós-transfundidos foram adequados independentemente do tipo sanguíneo do receptor ter sido igual ou não ao do doador. E a produção de aloanticorpos observada em alguns cães não interferiu em sua normalidade