Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

Estratégia, competências e desempenho em empresas de pet shop: evidências de um levantamento em Curitiba

No presente estudo, busca-se examinar a influência da combinação do ambiente percebido, das competências empresariais e do desempenho obtido na determinação da estratégia adotada por pequenas empresas representadas por lojas de comércio e prestação de serviços para animais de estimação - pet shops - em Curitiba (Paraná). A coleta de dados foi realizada por meio de um questionário estruturado dividido em cinco blocos. Foi possível identificar todos os quatro tipos de estratégia propostas pela tipologia de Miles e Snow (1978). A maioria das empresas pesquisadas adota a estratégia prospectora; em seguida aparecem as empresas que adotam a estratégia analítica e a estratégia defensiva; a postura reativa mostrou ser o comportamento estratégico menos adotado no setor. Na percepção dos respondentes, verificou-se que o ambiente do setor foi único, independentemente do tipo de estratégia adotada, caracterizando-se como complexo e pouco previsível; o mercado é dinâmico, mas mostra-se favorável ao crescimento. Em termos dos resultados organizacionais, apesar dos diferentes tipos de estratégia adotados, todos os respondentes afirmam, sem possibilidade de distinção, estar satisfeitos tanto com os resultados da gestão como com os resultados econômicos alcançados por suas empresas. Em termos de competências, o setor de pet shop enfatiza as competências gerenciais, as competências em serviços tradicionais e a competência em serviços de guarda de animais.

Journal of the Brazilian Chemical Society (JBCS): 10 anos da criação à consolidação

The main objectives of this article are to present and discuss the facts that lead to the conception of JBCS in 1987, its birth in 1990 and the stages traveled until its consolidation. The community's of Chemistry participation and the role of the Sub-program of Chemistry and Chemical Engineering of PADCT are emphasized.

Resultados científicos do cruzeiro do "Baependi" e do "Vega" à Ilha da Trindade: Hydrozoa

In Anis paper are listed 19 different species of Hydrozca collected during a trip to the oceanic island of Trindade, located at lat. 20º 30' 00" S. and long. 29º 22' 00" W., 600 miles off the brazilian coast. During the trip hawls and dredges were done at different points of the island and of banks that exist between the coast and the island. Of the 19 listed species one is here considered new to science: Hebellopsis besnardi (p. 83), characterized by having thecae with a single curvature and a strongly everted margin. Its measures are intermediate between those os H. hartmeyeri and H. sinuosa, which are its closest allies. H. besnardi was found epizoic on D. quadridentata. Of the remainder 18, 14 were already known from the brazilian coast. Of these 14, 4 were previously known only from the coast south of Cabo Frio, and 10 are at present known only from the region north of Cabo Frio. Five species are found both north and south of this Cape. As a whole, 5 species are recorded now for the first time on the brazilian coast, of these are given a full description and figures. This paper has the purpose of increasing the faunistical knowledge of this region of the Atlantic Ocean as a first step towards the understanding of the zoogeographical relationships with the other oceans and the establishment of the zoogeographical regions of this coast.

Cirurgia de resgate no carcinoma de canal anal

OBJETIVOS: Avaliar a sobrevida dos pacientes portadores de carcinoma epidermóide do canal anal submetidos a cirurgia de resgate, por recidiva ou falha do tratamento radioquimioterápico inicial. MÉTODO: Análise retrospectiva dos pacientes portadores de carcinoma epídermóide do canal anal submetidos a cirurgia de resgate, de outubro de 1986 a setembro de 2000. RESULTADOS: Foram matriculados 93 pacientes portadores de carcinoma epidermóide do canal anal no período, e 21 (22,5%) foram submetidos a resgate cirúrgico. Em 19 pacientes (91%) foi realizada amputação abdominoperineal do reto (operação de Miles), em um paciente exenteração pélvica total e em um paciente excisão local. Não houve mortalidade operatória. A sobrevida média do grupo após resgate cirúrgico foi de 24 meses. CONCLUSÕES: Após recidiva e/ou falha da radioquimioterapia, a cirurgia de resgate é importante no controle locorregional do carcinoma epidermóide do canal anal.

Advances in modelling of mechatronic systems: the toolset FASIM_C++ for the simulation of vehicle dynamics

The increasing complexity of controller systems, applied in modern passenger cars, requires adequate simulation tools. The toolset FASIM_C++, described in the following, uses complex vehicle models in three-dimensional vehicle dynamics simulation. The structure of the implemented dynamic models and the generation of the equations of motion applying the method of kinematic differentials is explained briefly. After a short introduction in methods of event handling, several vehicle models and applications like controller development, roll-over simulation and real-time-simulation are explained. Finally some simulation results are presented.

Effect of wave frequency on the nonlinear interaction between Görtler vortices and three-dimensional Tollmien-Schlichting waves

The nonlinear interaction between Görtler vortices (GV) and three-dimensional Tollmien-Schlichting (TS) waves nonlinear interaction is studied with a spatial, nonparallel model based on the Parabolized Stability Equations (PSE). In this investigation the effect of TS wave frequency on the nonlinear interaction is studied. As verified in previous investigations using the same numerical model, the relative amplitudes and growth rates are the dominant parameters in GV/TS wave interaction. In this sense, the wave frequency influence is important in defining the streamwise distance traveled by the disturbances in the unstable region of the stability diagram and in defining the amplification rates that they go through.

5-HT1A autoreceptor modulation of locomotor activity induced by nitric oxide in the rat dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is the origin of ascending serotonergic projections and is considered to be an important component of the brain circuit that mediates anxiety- and depression-related behaviors. A large fraction of DRN serotonin-positive neurons contain nitric oxide (NO). Disruption of NO-mediated neurotransmission in the DRN by NO synthase inhibitors produces anxiolytic- and antidepressant-like effects in rats and also induces nonspecific interference with locomotor activity. We investigated the involvement of the 5-HT1A autoreceptor in the locomotor effects induced by NO in the DRN of male Wistar rats (280-310 g, N = 9-10 per group). The NO donor 3-morpholinosylnomine hydrochloride (SIN-1, 150, and 300 nmol) and the NO scavenger S-3-carboxy-4-hydroxyphenylglycine (carboxy-PTIO, 0.1-3.0 nmol) were injected into the DRN of rats immediately before they were exposed to the open field for 10 min. To evaluate the involvement of the 5-HT1A receptor and the N-methyl-D-aspartate (NMDA) glutamate receptor in the locomotor effects of NO, animals were pretreated with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 8 nmol), the 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635, 0.37 nmol), and the NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 nmol), followed by microinjection of SIN-1 into the DRN. SIN-1 increased the distance traveled (mean ± SEM) in the open-field test (4431 ± 306.1 cm; F7,63 = 2.44, P = 0.028) and this effect was blocked by previous 8-OH-DPAT (2885 ± 490.4 cm) or AP7 (3335 ± 283.5 cm) administration (P < 0.05, Duncan test). These results indicate that 5-HT1A receptor activation and/or facilitation of glutamate neurotransmission can modulate the locomotor effects induced by NO in the DRN.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.