Abstract Background: The resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. Methods: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Results: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 μM to 19.11 μM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.

El estudio del proceso de combustión en motores Diésel ha sido, durante años, un tema de gran interés debido principalmente a la creciente necesidad de mejorar el rendimiento de los motores, reducir el consumo de combustible y reducir la emisión de contaminantes. Los estudios experimentales presentan la desventaja de requerir grandes recursos económicos y tiempo en su realización, razón por la cual se utilizan modelos computacionales que permiten estudiar el proceso de combustión de una forma más económica y práctica. En este artículo se presenta una revisión de varios de los modelos de combustión en motores Diésel más relevantes, desarrollados a nivel nacional e internacional, con el fin de dar al lector una visión de la evolución y el estado actual de este tipo de modelos.

The study of the combustion process in Diesel engines has been for years a subject of great interest mainly due to the increasing need to improve engine performance, reduce fuel consumption and reduce the pollutant emissions. Experimental studies have the disadvantage of require enormous efforts, money and time, that is the reason why computer models are used to study the combustion process in a more economical and practical way. This article presents a review of the most relevant Diesel engine combustion models developed nationally and internationally, to give the reader an insight of the evolution and current status of such models.

Este artículo presenta el desarrollo de un controlador de tráfico difuso capaz de gestionar de manera autónoma, centralizada y eficiente, el flujo vehicular en un grupo de intersecciones. El sistema emplea un algoritmo de visión artificial que le permite detectar el número de autos presentes en imágenes capturadas por un conjunto de cámaras estratégicamente ubicadas en cada intersección. Usando esta información, el sistema selecciona la secuencia de acciones que optimicen el flujo vehicular dentro de la zona de control, en un escenario simulado. Los resultados obtenidos muestran que el sistema disminuye en un 20% los tiempos de retraso para cada vehículo y que además es capaz de adaptarse rápida y eficientemente a los cambios de flujo.

This paper presents a fuzzy traffic controller that in an autonomous, centralized and efficient way, manages vehicular traffic flow in a group of intersections. The system uses a computer vision algorithm to detect the number of cars in images captured by a set of strategically placed cameras at every intersection. Using this information, the system selects the sequence of actions that optimize traffic flow within the control area, in a simulated scenario. The results obtained show that the system reduces the delay times for each vehicle by 20% and that the controller is able to adapt smoothly to different flow changes.

INTRODUÇÃO: O tratamento percutâneo com cateter-balão e stents não-farmacológicos (SNF) de lesões na artéria descendente anterior (DA), quando comparado ao tratamento das outras artérias epicárdicas, freqüentemente cursa com taxas maiores de reestenose, comprometendo o resultado tardio da abordagem percutânea. OBJETIVO: Comparar a segurança e a eficácia tardia dos stents farmacológicos (SF) versus os SNF no tratamento de lesões únicas na DA. MÉTODO: Entre junho de 2002 e junho de 2003, 166 pacientes com lesão única em DA foram tratados com SF e comparados a uma coorte histórica de 141 pacientes tratados com SNF sob os mesmos critérios de inclusão/exclusão. Seguimento clínico tardio (aproximadamente dois anos) foi obtido em todos os pacientes. Objetivou-se comparar a taxa de eventos cardíacos adversos maiores (ECAM), definidos como morte cardíaca, infarto do miocárdio e revascularização da lesão-alvo (RLA), entre os dois grupos. RESULTADOS: Os grupos não diferiram quanto às características basais. O sucesso do procedimento foi obtido em todos os casos, não havendo eventos maiores na fase intra-hospitalar. Ao final de dois anos, 95,7% dos pacientes tratados com SF e 73,7% dos que receberam SNF estavam livres de ECAM (p < 0,0001). RLA ocorreu em 15,6% e 1,2% dos pacientes tratados com SNF e SF, respectivamente (p < 0,0001). Ainda que não significativa, a mortalidade cardíaca foi maior no grupo que recebeu SNF, comparativamente ao que recebeu SF (6,38% vs. 1,81%, respectivamente; p = 0,07). CONCLUSÃO: O implante de SF para o tratamento de lesões únicas na DA mostrou-se superior ao de SNF, reduzindo de forma significativa a taxa de ECAM, sobretudo a necessidade de nova RLA.

INTRODUCTION: Percutaneous treatment (PCI) of single lesions in the LAD with balloon angioplasty or bare-metal stent (BMS) often have poorer outcomes when compared to PCI of lesions in the other major coronary arteries. OBJECTIVE: To compare the long term safety and efficacy of DES vs. BMS for the treatment of single lesions in the LAD. METHODS: Between June 2002 and June 2003, 166 patients with single lesions in the LAD were treated with DES and compared to a historic cohort of 141 patients treated with BMS under the same inclusion/exclusion criteria. Long term clinical follow-up (approximately 2 years) was obtained in all patients. The primary endpoint was the comparison of major adverse cardiac events (MACE) defined as cardiac death, non fatal MI and target-lesion revascularization (TLR) between the two groups. RESULTS: Baseline clinical characteristics did not differ between groups. Procedure success was achieved in all cases with no in hospital MACE. After two years of follow-up, 95.7% of patients treated with DES and 73.7% treated with BMS were free from any MACE (p < 0.0001). TLR occurred in 15.6% and 1.2% of the patients receiving BMS and DES respectively (p < 0.0001). Although not significantly reduced, cardiac death was less frequent among patients treated with these DES (6.38% vs. 1.81%, p = 0.07). CONCLUSION: The use of DES for the treatment of single LAD lesions was superior to BMS due to a marked reduction in MACE rates, mainly at the expense of a very low need for RLA.

Background: Employing molecular epidemiology techniques for the study of tuberculosis can afford the possibility of identifying tuberculosis transmission patterns. This study has been made for the purpose of estimating the incidence of tuberculosis related to recent transmission in Madrid and of identifying the risk factors making it possible to define transmission patterns. Methods: A three-year descriptive populational study was conducted on patients diagnosed with tuberculosis based on cultures in four districts in Madrid (550,442 inhabitants). The transmission patterns were described by means of conventional epidemiological research and molecular techniques (Restriction Fragment Length Polymorphism - RFLP- analysis with IS6110 and spoligotyping). Results: An RFLP analysis was conducted on 233 clinically isolated Mycobacterium tuberculosis strains, 99 (42.5%) of which were grouped into 29 clusters. The most numerous group was comprised of 134 patients infected with M. tuberculosis strains of a single RFLP pattern. These patients averaged 48.3 years of age (DE 19.4), and 17.2% were revealed to have an endogenous risk factor. Two transmission patterns were identified among the grouped cases. The first pattern included 57 patients pertaining to 23 small clusters (2-4 cases), 25 (43.9%) of which were epidemiologically linked to another case from the same cluster. The second pattern was comprised of 42 patients grouped into 6 large clusters (5 cases or more). The subjects averaged 31.4 years of age (DE 15.8), 28.6% being intravenous drug users, 31% infected with HIV, and 26.2% having a prison background. Conclusions: Identifying tuberculosis transmission patterns by using molecular biology techniques affords the possibility of detecting population groups for whom preferential measures can be taken in the prevention and control programs.

Fundamento: La aplicación de las técnicas de epidemiología molecular en el estudio de la tuberculosis puede permitir identificar los patrones de transmisión de la enfermedad. El objetivo de este estudio ha sido estimar la incidencia de tuberculosis asociada a transmisión reciente en Madrid e identificar los factores de riesgo que permitan definir patrones de transmisión. Métodos: Se realizó un estudio descriptivo poblacional de tres años de duración en pacientes diagnosticados de tuberculosis mediante cultivo en cuatro distritos de Madrid (550.442 habitantes). La descripción de los patrones de transmisión se realizó mediante la investigación epidemiológica convencional y las técnicas moleculares (análisis de fragmentos de restricción de longitud polimórfica -RFLP- con IS6110 y spoligotyping). Resultados: Se realizó RFLP en 233 aislados clínicos de Mycobacterium tuberculosis, de los que 99 (42,5%) estaban agrupados en 29 clusters. El grupo más numeroso lo formaban 134 enfermos infectados por cepas de M. tuberculosis con patrón RFLP único. Su media de edad era 48,3 años (DE 19,4) y el 17,2% presentaba un factor de riesgo de reactivación endógena. Entre los casos agrupados se identificaron dos patrones de transmisión. El primero de ellos incluía a 57 enfermos pertenecientes a 23 clusters pequeños (2-4 casos), de los que 25 (43,9%) estaban conectados epidemiológicamente con otro caso de su mismo cluster. El segundo lo formaban 42 pacientes agrupados en 6 clusters grandes (5 casos o más). La media de edad era de 31,4 años (DE 15,8), el 28,6% eran usuarios de drogas inyectadas, el 31% estaban infectados por el VIH, y el 26,2% tenían antecedentes de estancia en prisión. Conclusiones: La identificación de patrones de transmisión de la tuberculosis utilizando técnicas de biología molecular permite detectar grupos de población susceptibles de actuación preferente en los programas de prevención y control.

Background: Employing molecular epidemiology techniques for the study of tuberculosis can afford the possibility of identifying tuberculosis transmission patterns. This study has been made for the purpose of estimating the incidence of tuberculosis related to recent transmission in Madrid and of identifying the risk factors making it possible to define transmission patterns. Methods: A three-year descriptive populational study was conducted on patients diagnosed with tuberculosis based on cultures in four districts in Madrid (550,442 inhabitants). The transmission patterns were described by means of conventional epidemiological research and molecular techniques (Restriction Fragment Length Polymorphism - RFLP- analysis with IS6110 and spoligotyping). Results: An RFLP analysis was conducted on 233 clinically isolated Mycobacterium tuberculosis strains, 99 (42.5%) of which were grouped into 29 clusters. The most numerous group was comprised of 134 patients infected with M. tuberculosis strains of a single RFLP pattern. These patients averaged 48.3 years of age (DE 19.4), and 17.2% were revealed to have an endogenous risk factor. Two transmission patterns were identified among the grouped cases. The first pattern included 57 patients pertaining to 23 small clusters (2-4 cases), 25 (43.9%) of which were epidemiologically linked to another case from the same cluster. The second pattern was comprised of 42 patients grouped into 6 large clusters (5 cases or more). The subjects averaged 31.4 years of age (DE 15.8), 28.6% being intravenous drug users, 31% infected with HIV, and 26.2% having a prison background. Conclusions: Identifying tuberculosis transmission patterns by using molecular biology techniques affords the possibility of detecting population groups for whom preferential measures can be taken in the prevention and control programs.

Fundamento: La aplicación de las técnicas de epidemiología molecular en el estudio de la tuberculosis puede permitir identificar los patrones de transmisión de la enfermedad. El objetivo de este estudio ha sido estimar la incidencia de tuberculosis asociada a transmisión reciente en Madrid e identificar los factores de riesgo que permitan definir patrones de transmisión. Métodos: Se realizó un estudio descriptivo poblacional de tres años de duración en pacientes diagnosticados de tuberculosis mediante cultivo en cuatro distritos de Madrid (550.442 habitantes). La descripción de los patrones de transmisión se realizó mediante la investigación epidemiológica convencional y las técnicas moleculares (análisis de fragmentos de restricción de longitud polimórfica -RFLP- con IS6110 y spoligotyping). Resultados: Se realizó RFLP en 233 aislados clínicos de Mycobacterium tuberculosis, de los que 99 (42,5%) estaban agrupados en 29 clusters. El grupo más numeroso lo formaban 134 enfermos infectados por cepas de M. tuberculosis con patrón RFLP único. Su media de edad era 48,3 años (DE 19,4) y el 17,2% presentaba un factor de riesgo de reactivación endógena. Entre los casos agrupados se identificaron dos patrones de transmisión. El primero de ellos incluía a 57 enfermos pertenecientes a 23 clusters pequeños (2-4 casos), de los que 25 (43,9%) estaban conectados epidemiológicamente con otro caso de su mismo cluster. El segundo lo formaban 42 pacientes agrupados en 6 clusters grandes (5 casos o más). La media de edad era de 31,4 años (DE 15,8), el 28,6% eran usuarios de drogas inyectadas, el 31% estaban infectados por el VIH, y el 26,2% tenían antecedentes de estancia en prisión. Conclusiones: La identificación de patrones de transmisión de la tuberculosis utilizando técnicas de biología molecular permite detectar grupos de población susceptibles de actuación preferente en los programas de prevención y control.