Targeting lactate transport suppresses in vivo breast tumour growth.

BACKGROUND Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. RESULTS The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. CONCLUSIONS This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

Estudo da série histórica de mortalidade por suicídio no Espírito Santo (de 1980 a 2006)

OBJETIVO: Estudar a série histórica de suicídio no Estado do Espírito Santo (1980 a 2006) e suas estratificações. MÉTODOS: Estudo descritivo, retrospectivo, de série histórica. Foram incluídos os óbitos registrados no Sistema de Informação sobre Mortalidade como suicídio, de residentes no Espírito Santo (1980 a 2006). Foram construídas as séries históricas e calculados os coeficientes de mortalidade por suicídio para o período. Procedeu-se à padronização das taxas de mortalidade pelo método direto, em que a população do censo IBGE-2000 foi considerada padrão. Para cálculo das taxas, utilizou-se o Programa Excel 7.0. As equações de tendência linear e as estatísticas de ajuste de modelo (valor de R² e o valor p do teste F de adequação do modelo) foram obtidas do programa Statistical Package for Social. Sciences. O nível de significância adotado foi de 5%. RESULTADOS: A tendência de crescimento das taxas de suicídio no Estado foi de 24,9%. Para os homens, essa tendência de crescimento foi de 23,8%. As faixas etárias com tendência de crescimento foram aquelas entre 10 e 14 anos e acima de 30 anos até 59 anos. CONCLUSÃO: O suicídio foi mais frequente entre os homens, e as principais faixas etárias com tendência de crescimento foram aquelas entre 30 e 59 anos.

António Rodrigues Sampaio e o papel “civilizador” da imprensa

António Rodrigues Sampaio foi seguramente um dos maiores e melhores jornalistas portugueses do século XIX, tendo exercido longamente a profissão, sobretudo em “A Revolução de Setembro”, como um verdadeiro magistério cívico e político. Nesta comunicação procura-se sublinhar as concepções jornalísticas desta figura oitocentista, perspectivadas no quadro a que José Tengarrinha chamou a ‘fase romântica da Imprensa portuguesa. Sustenta-se aqui a ideia de que as tribunas jornalísticas e o próprio jornalismo eram assumidos por Rodrigues Sampaio como formas desejáveis e eficazes de transferir para o debate das ideias a violência das relações sociais, originadas pelas mudanças culturais, económicas e políticas. O jornalismo seria uma forma de prosseguir a guerra por outros meios, parafraseando Clausewitz.

D. António Barroso e as potencialidades do turismo religioso em Remelhe (Barcelos, norte de Portugal)

Dissertação de mestrado em Património e Turismo Cultural

Contributo para a compreensão das causas de exclusão de ilicitude e da culpa no crime de acesso ilegítimo

Dissertação de mestrado em Direito e Informática

Gestão integrada dos recursos hídricos da região de Fafe: caracterização da qualidade das águas superficiais, potencial hidrogeológico das rochas fraturadas

Dissertação de mestrado em Geociências (área de especialização em Recursos Geológicos)

Trends in mortality due to ischemic heart disease in the municipality of Goiania, Brazil, during the years between 1980 and 1994

OBJECTIVE: To analyze the trends of specific, standardized coefficients of mortality due to ischemic heart disease according to sex and age during the years 1980 and 1994 in the municipality of Goiania, GO, Brazil. METHODS: Data on deaths were retrieved from the Information on Mortality System of the Ministry of Health; population data were obtained from the Foundation of the Brazilian Institute for Geography and Statistics (IBGE). The trends of the specific coefficients were analyzed by triennia of the historical series, including individuals of both sexes from 25 years of age on, partitioned into 6 age groups of ten years intervals. The population data corresponding to the year 1980 were used as the standard for the calculation of each age group coefficient. Analyses were carried out by straight linear regression. RESULTS: Coefficients were greater for males in each triennium of the series and increased with age in both sexes. The study of the trends of the specific age coefficients of both sexes revealed a stable pattern of evolution up to the age of 65-74 years (P>0.05). From 75 years on, a clear-cut decline in mortality due to ischemic heart disease was shown by both sexes. The standardized coefficients also showed a significant decline (p<=0.05). CONCLUSION: The municipality of Goiânia is at present in a stage of epidemiological transition similar to that of developed countries, even though the observed decline is predominantly influenced by the mortality of older individuals (75 years of age or older).

Does a circadian variation occur in myocardial ischemia over 48 hours in patients with unstable angina?

OBJECTIVE: To study the incidence of and variation in myocardial ischemia over 48 hours in patients with unstable angina. METHODS: Thirty-nine patients with unstable angina underwent long-term electrocardiography for 48 hours. The number of events and the period of time of ischemia (in minutes) were analyzed for the 48 hours, in two periods of 24 hours, and in periods of 4 hours. RESULTS: We analyzed 1755.8 hours of monitoring tapes, and ischemic episodes were detected in 18 (46.2%) patients, corresponding to 173 ischemic episodes, allowing the evaluation of 1304 minutes of ischemia.only 4 of which were (2.2%) symptomatic, Considering the entire period of time of recording and the predetermined time intervals, we observed a higher number of ischemic episodes (38) and a longer duration of ischemia (315.4 minutes) between 11:00 am and 3:00 pm. However, no significant differences occurred among the values in the different intervals. CONCLUSION: Long-term electrocardiography over 48 hours showed a high incidence (97.8%) of silent ischemic episodes in patients with unstable angina. No evidence of a circadian variation of myocardial ischemia in unstable angina was observed.

Trends of the Risk of Death due to Circulatory, Cerebrovascular, and Ischemic Heart Diseases in 11 Brazilian Capitals from 1980 to 1998

OBJECTIVE: To assess the trends of the risk of death due to circulatory (CD), cerebrovascular (CVD), and ischemic heart diseases (IHD) in 11 Brazilian capitals from 1980 to 1998. METHODS: Data on mortality due to CD, CVD and IHD were obtained from the Brazilian Health Ministry, and the population estimates were calculated by interpolation with the Lagrange method based on census data from 1980 and 1991 and the population count of 1996. The trends were analyzed with the multiple linear regression method. RESULTS: CD showed a trend towards a decrease in most capitals, except for Brasília, where a mild increase was observed. The cities of Porto Alegre, Curitiba, Rio de Janeiro, Cuiabá, Goiânia, Belém, and Manaus showed a decrease in the risk of death due to CVD and IHD, while the city of Brasília showed an increase in CVD and IHD. The city of São Paulo showed a mild increase in IHD for individuals of both sexes aged 30 to 39 years and for females aged 40 to 59 years. In the cities of Recife and Salvador, a reduction in CD was observed for all ages and both sexes. In the city of Recife, however, an increase in IHD was observed at younger ages (30 to 49 years), and this trend decreased until a mild reduction (-4%) was observed in males ³ 70 years. CONCLUSION: In general, a reduction in the risk of death due to CD and an increase in IHD were observed, mainly in the cities of Recife and Brasília.

Plantae Wilsonianae :an enumeration of the woody plants collected in western China for the Arnold arboretum of Harvard university during the years 1907, 1908, and 1910 /by E. H. Wilson, ed. by Charles Sprague Sargent.

1916 v.2

Plantae Wilsonianae :an enumeration of the woody plants collected in western China for the Arnold arboretum of Harvard university during the years 1907, 1908, and 1910 /by E. H. Wilson, ed. by Charles Sprague Sargent.

1917 v.3

Plantae Wilsonianae :an enumeration of the woody plants collected in western China for the Arnold arboretum of Harvard university during the years 1907, 1908, and 1910 /by E. H. Wilson, ed. by Charles Sprague Sargent.

1913 v.1

Medical care and deaths due to coronary artery disease in Brazil, 1980-1999

OBJECTIVE: To estimate the frequency of medical care preceding deaths due to coronary artery diseases (CAD) in different Brazilian regions and capitals and to describe trends in medical care from 1980 to 1999. METHODS: Information on medical care preceding deaths due to coronary artery diseases/acute myocardial infarction in adults > 20 years from 1980 to 1999 was collected in the DATASUS, the databank of the Brazilian Health Ministry. Sex, states, and capitals selected for 1999 were analyzed in the study. Medical care was stratified as follows: with, without, and ignored medical care. The descriptive analysis comprised frequencies, ratios of frequency, test for proportions, and increments or reductions in frequencies. RESULTS: Acute myocardial infarction (AMI) represented 75 to 85% of the CAD in the period; the frequency of deaths with medical care ranged from 48.9 to 63%, and that of ignored medical care ranged from 27.2 to 41.5%. The frequency of other CAD with medical care ranged from 56 to 76%. The frequency of deaths preceded by medical care decreased by 17.8%, and that with ignored medical care increased by 36.5% (RF=2). The values for the other CAD were -20.2% and +64.6% (RF=44.4). Deaths preceded by medical care were more frequent in females at all ages and in all Brazilian regions. CONCLUSION: The results show a high frequency of sudden death and suggest errors in diagnosis or codification and overestimation of the statistics about mortality. Validation of the death certificate diagnosis and frequent surveillance are required.