Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum

We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y6 receptor antagonist, and mimicked by PSB 0474, P2Y6-receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin, but not by MRS 2578, whilst the inhibitory effects were antagonized by PPADS but not by suramin or MRS 2578. UTPγS, P2Y2/4 receptor agonist but not 2-thio-UTP, P2Y2 receptor agonist, mimicked UTP effects. The inhibitory effects induced by UTP was abolished by ATP desensitization and increased by extracellular acidification. UDP or UTP responses were insensitive to TTX, atropine, or L-NAME antagonized by U-73122, inhibitor of phospholipase C (PLC) and preserved in the presence of nifedipine or low Ca2+ solution. Transcripts encoding the uracil nucleotide-preferring receptors were expressed in mouse ileum. Functional postjunctional uracil-sensitive receptors are present in the longitudinal muscle of the mouse ileum. Activation of P2Y6 receptors induces muscular contraction, whilst activation of P2Y4 receptors leads to inhibition of the contractile activity. Indeed, the presence of atypical UTP-sensitive receptors leading to muscular contraction is suggested. All uracil-sensitive receptors are linked to the PLC pathway

Equações de predição da aptidão cardiorrespiratória sem testes de exercício e sua aplicabilidade em estudos epidemiológicos: uma revisão sistemática Prediction of aerobic fitness without stress testing and applicability to epidemiological studies: a systematic review

Uma baixa aptidão cardiorrespiratória é considerada fator de risco independente para o óbito por todas as causas, mas principalmente por doença coronariana. Devido a essa importância e à dificuldade de avaliá-la por meio de testes de exercícios, formas alternativas de avaliação foram sugeridas, envolvendo equações de predição sem a necessidade de realização de exercícios. O presente estudo objetivou analisar criticamente esses modelos e, principalmente, sua aplicabilidade em estudos epidemiológicos. Foi realizada uma revisão de artigos publicados entre 1966 e 2002. Os critérios para julgar a qualidade dos estudos foram: (a) inclusão de variáveis explicativas com base teórica; (b) critérios de validação (padrão-ouro); (c) equações apresentadas por completo, incluindo erro padrão da estimativa; (d) equações submetidas a processo de validação cruzada. Apenas cinco dos 23 estudos selecionados atenderam a todos os critérios de qualidade. Conclui-se que, em princípio, os modelos sem exercícios podem constituir alternativa viável para avaliação da aptidão cardiorrespiratória em estudos epidemiológicos. No entanto, ainda são poucas as equações disponíveis cuja validação permite grau aceitável de generalização.<br>Cardiorespiratory fitness is used as an independent factor for evaluating risk of all-cause mortality, but mainly from coronary heart disease. Nevertheless, evaluation of fitness based on stress tests poses numerous epidemiological difficulties. Alternative forms of evaluation have therefore been suggested using non-exercise-based regression models. This study aimed to analyze these models and their applicability to epidemiological studies. A systematic review was conducted of articles published from 1966 to 2002. The models were classified according to: (a) theoretical justification for the explanatory variables included in the model; (b) validation criteria (gold standard); (c) regression models fully reported, including standard error of estimation; and (d) cross-validation. The search process yielded 23 studies, five of which met all established quality criteria. The authors conclude that cardiorespiratory evaluation by non-exercise-based models could be feasible in epidemiological studies. However, few equations appear to meet the minimum external validation requirements to provide data that could be generalized to large populations

A comprehensive review of Toxoplasma gondii biology and host-cell interaction: Challenges for a plant-based vaccine

Toxoplasmosisis a worldwide-distributed infection caused by Toxoplasma gondii, which causes a wide range of clinical syndromesin humans, mammals and birds. T. gondiiis considered a parasite of veterinary and medical importance, because it maycause abortion or congenital disease in its intermediate hosts. Despite theeconomic losses associated with T. gondiiinfection in farm animals and the socio-economic impact caused by this zoonoticdisease in the human population, there is no effective treatment available forhumans or animals able to eliminate the parasite from the host once the chronicinfection has been established. The only commercial vaccine is the S48 strainof attenuated tachyzoites for use in sheep. However, this vaccine causes sideeffects, has a short life time and induces a short-term immunity. So far, noacellular vaccine against toxoplasmosis has been commercialized. In fact, futurechallenges include the development of an effective vaccine to preventtoxoplasmosis. Most parasitologists and vaccinologists agree that futureefforts should be concentrated on developing multi-antigen vaccines and moreefficient delivery systems able to express heterologous proteins abundantly aswell as on searching for immunization schedules and adequate adjuvants toenhance the protective responses. To achieve this, platforms for the productionof acellular vaccines based on the use of plants can have an important role.Fil: Sander, Valeria Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ángel, Sergio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Clemente, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin