Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

Water residence time affecting phytoplankton blooms: study case in Ibitinga Reservoir (São Paulo, Brazil) using Landsat/TM images / Efeito de variações no tempo de residência hidráulica sobre a ocorrência de florações de fitoplâncton: estudo de caso no Reservatório de Ibitinga (SP) com o uso de imagens Landsat/TM

Abstract Satellite images are an effective tool for the detection of phytoplankton blooms, since they cause striking changes in water color. Bloom intensity can be expressed in terms of chlorophyll-a concentration. Previous studies suggest the use of Landsat TM4/TM3 reflectance ratio to retrieve surface chlorophyll-a concentration from aquatic systems. In this study we assumed that a remote sensing trophic state index can be applied to investigate how changes in HRT along the hydrologic year affect the spatial distribution of the phytoplankton blooms at Ibitinga’s reservoir surface. For that, we formulated two objectives: (1) apply a semi-empirical model which uses this reflectance ratio to map chlorophyll-a concentration at Ibitinga reservoir along the 2005 hydrologic year and (2) assess how changes in hydraulic residence time (HRT) affect the spatial distribution of phytoplankton blooms at Ibitinga Reservoir. The study site was chosen because previous studies reported seasonal changes in the reservoir limnology which might be related to the reservoir seasonality and hydrodynamics. Six Landsat/TM images were acquired over Ibitinga reservoir during 2005 and water flow measurements provided by the Brazilian Electric System National Operator - ONS were used to compute the reservoir´s residence time, which varied from 5.37 to 52.39 days during 2005. The HRT in the date of image acquisition was then compared to the distribution of chlorophyll-a in the reservoir. The results showed that the HRT increasing implies the increasing of the reservoir surface occupied by phytoplankton blooms.

Resumo As imagens de satélite são frequentemente usadas para a identificação de florações de fitoplâncton porque sua presença causa mudanças significativas na cor da água. A abundância das florações pode ser quantificada por medidas de concentração de clorofila-a. Diversos estudos sugerem o uso da razão de reflectância das bandas TM4/TM3 Landsat, para determinar as concentrações de clorofila-a em sistemas aquáticos. Este trabalho tem como objetivos: (1) aplicar um modelo semi-empírico que usa essa razão para mapear a concentração de clorofila-a no reservatório de Ibitinga ao longo do ano hidrológico de 2005; (2) avaliar como as mudanças no tempo de residência hidráulica afetaram a distribuição de florações na superfície do reservatório. O reservatório de Ibitinga foi selecionado porque estudos prévios indicavam mudanças sazonais nas propriedades limnológicas do reservatório, as quais poderiam estar relacionadas à sazonalidade e à hidrodinâmica. Seis imagens TM/Landsat foram adquiridas sobre o reservatório de Ibitinga durante o ano de 2005. Foi então usada uma tabela associando intervalos de razão de banda a intervalos de concentração de clorofila-a. Medidas de vazão fornecidas pelo Operador Nacional do Sistema Elétrico – ONS foram utilizadas para calcular o tempo de residência hidráulica do reservatório, que variou entre 5,37 e 52,39 dias durante 2005. O tempo de residência hidráulica em cada data de aquisição da imagem foi então comparado com a área ocupada pelas florações de fitoplancton. Os resultados indicaram uma forte relação entre o tempo de residência hidráulica e a área ocupada por florações. Em junho de 2005, quando o reservatório atingiu seu menor tempo de residência hidráulica, apenas 20% de sua área estiveram ocupadas por florações. Em setembro e outubro, quando a residência hidráulica atinge o seu máximo, mais que 80% da superfície do reservatório foram ocupadas por florações de fitoplancton.

Water residence time affecting phytoplankton blooms: study case in Ibitinga Reservoir (São Paulo, Brazil) using Landsat/TM images.

Satellite images are an effective tool for the detection of phytoplankton blooms, since they cause striking changes in water color. Bloom intensity can be expressed in terms of chlorophyll-a concentration. Previous studies suggest the use of Landsat TM4/TM3 reflectance ratio to retrieve surface chlorophyll-a concentration from aquatic systems. In this study we assumed that a remote sensing trophic state index can be applied to investigate how changes in HRT along the hydrologic year affect the spatial distribution of the phytoplankton blooms at Ibitinga's reservoir surface. For that, we formulated two objectives: (1) apply a semi-empirical model which uses this reflectance ratio to map chlorophyll-a concentration at Ibitinga reservoir along the 2005 hydrologic year and (2) assess how changes in hydraulic residence time (HRT) affect the spatial distribution of phytoplankton blooms at Ibitinga Reservoir. The study site was chosen because previous studies reported seasonal changes in the reservoir limnology which might be related to the reservoir seasonality and hydrodynamics. Six Landsat/TM images were acquired over Ibitinga reservoir during 2005 and water flow measurements provided by the Brazilian Electric System National Operator - ONS were used to compute the reservoir´s residence time, which varied from 5.37 to 52.39 days during 2005. The HRT in the date of image acquisition was then compared to the distribution of chlorophyll-a in the reservoir. The results showed that the HRT increasing implies the increasing of the reservoir surface occupied by phytoplankton blooms.

Abiotic variability among different aquatic systems of the central Amazon floodplain during drought and flood events.

This paper examines water properties from lakes, (depression lakes, sensu Junk et al., 2012), channels (scroll lakes with high connectivity, sensu Junk et al., 2012) and paleo-channels (scroll lakes with low connectivity-sensu Junk et al., 2012, locally called ressacas) located in Mamirauá Sustainable Development Reserve, in Central Amazon floodplain, Amazonas, Brazil. We analysed surface temperature, conductivity, pH, dissolved oxygen, turbidity, transparency, suspended inorganic and organic matter, chlorophyll-a, pheophytin, total nitrogen, total phosphorus, organic and inorganic carbon in 2009 high water phase, 2009 and 2010 low water phases. Multivariate statistical analyses of 24 aquatic systems (6 ressacas, 12 lakes and 6 channels, 142 samples) were applied to the variables in order to: 1) quantify differences among aquatic system types; 2) assess how those differences are affected in the different phases of the hydrological year. First, we analysed the entire set of variables to test for differences among phases of the hydrological year and types of aquatic systems using a PERMANOVA two-way crossed design. The results showed that the all measured limnological variables are distinct regarding both factors: types of aquatic systems and hydrological phases. In general, the magnitude and amplitude of all variables were higher in the low water phase than in the high water phase, except for water transparency in all aquatic system's types. PERMANOVA showed that the differences between aquatic system's types and hydrological phases of all variables were highly significant for both main factors (type and phase) and for the type x phase interaction. Limnological patterns of Amazon floodplain aquatic systems are highly dynamic, dependent on the surrounding environment, flood pulse, main river input and system type. These patterns show how undisturbed systems respond to natural variability in such a diverse environment, and how distinct are those aquatic systems, especially during the low water phase. Aquatic systems in Mamirauá floodplain represent limnological patterns of almost undisturbed areas and can be used as future reference for comparison with disturbed areas, such as those of the Lower Amazon, and as a baseline for studies on the effects of anthropogenic influences and climate change and on Amazon aquatic ecosystem.

Abiotic variability among different aquatic systems of the central Amazon floodplain during drought and flood events / Variabilidade abiótica entre os diferentes sistemas aquáticos da planície de inundação da Amazônia central durante eventos de seca e cheia

Abstract This paper examines water properties from lakes, (depression lakes, sensu Junk et al., 2012), channels (scroll lakes with high connectivity, sensu Junk et al., 2012) and paleo-channels (scroll lakes with low connectivity-sensu Junk et al., 2012, locally called ressacas) located in Mamirauá Sustainable Development Reserve, in Central Amazon floodplain, Amazonas, Brazil. We analysed surface temperature, conductivity, pH, dissolved oxygen, turbidity, transparency, suspended inorganic and organic matter, chlorophyll-a, pheophytin, total nitrogen, total phosphorus, organic and inorganic carbon in 2009 high water phase, 2009 and 2010 low water phases. Multivariate statistical analyses of 24 aquatic systems (6 ressacas, 12 lakes and 6 channels, 142 samples) were applied to the variables in order to: 1) quantify differences among aquatic system types; 2) assess how those differences are affected in the different phases of the hydrological year. First, we analysed the entire set of variables to test for differences among phases of the hydrological year and types of aquatic systems using a PERMANOVA two-way crossed design. The results showed that the all measured limnological variables are distinct regarding both factors: types of aquatic systems and hydrological phases. In general, the magnitude and amplitude of all variables were higher in the low water phase than in the high water phase, except for water transparency in all aquatic system’s types. PERMANOVA showed that the differences between aquatic system’s types and hydrological phases of all variables were highly significant for both main factors (type and phase) and for the type x phase interaction. Limnological patterns of Amazon floodplain aquatic systems are highly dynamic, dependent on the surrounding environment, flood pulse, main river input and system type. These patterns show how undisturbed systems respond to natural variability in such a diverse environment, and how distinct are those aquatic systems, especially during the low water phase. Aquatic systems in Mamirauá floodplain represent limnological patterns of almost undisturbed areas and can be used as future reference for comparison with disturbed areas, such as those of the Lower Amazon, and as a baseline for studies on the effects of anthropogenic influences and climate change and on Amazon aquatic ecosystem.

Resumo Esse trabalho investiga as propriedades da água de lagos (lagos de depressão, sensu Junk et al., 2012), canais (scroll lakes com alta conectividade, sensu Junk et al., 2012) e paleo canais (scroll lakes com baixa conectividade - sensu Junk et al., 2012, localmente chamados de ressaca) localizados na Reserva de Desenvolvimento Sustentável Mamirauá (RDSM), na planície de inundação da Amazônia Central, Amazonas, Brasil. Analisaram-se temperatura, condutividade, pH, oxigênio dissolvido, turbidez, e transparência da água na superfície e coletaram-se amostras de água na superfície para a determinação de material orgânico e inorgânico em suspensão, clorofila-a, feofitina, nitrogênio e fósforo total, carbono orgânico e inorgânico dissolvido, em duas fases da hidrógrafa, água alta em 2009, e água baixa em 2009 e 2010. Análises de estatística multivariada de 24 sistemas aquáticos (6 ressacas, 12 lagos e 6 canais, 142 amostras) foram realizadas para: 1) quantificar as diferenças entre os tipos de sistemas aquáticos; 2) determinar como essas diferenças são afetadas nas diferentes fases do ano hidrológico. Primeiramente foram analisadas todas as variáveis para testar as diferenças entre as fases do ano hidrológico e dos tipos de sistemas aquáticos utilizando o teste pareado cruzado PERMANOVA. Os resultados mostraram que todas as variáveis limnológicas medidas são distintas em relação a ambos os fatores: tipos de sistemas aquáticos e fases da hidrógrafa. Em geral, a magnitude e amplitude de todas as variáveis foram maiores na fase seca do que na cheia, com exceção da transparência da água em todos os tipos de sistemas aquáticos. Os resultados da PERMANOVA mostraram que as diferenças entre os tipos de sistemas aquáticos e as fases da hidrógrafa para todas as variáveis foram altamente significativas para ambos os fatores (tipo e fase) e ainda para a interação tipo x fase. Os padrões limnológicos dos sistemas aquáticos da planície de inundação Amazônica são altamente dinâmicos, dependente do ambiente ao redor, do pulso de inundação, do rio principal e do tipo de sistema. Os sistemas aquáticos da planície de inundação de Mamirauá representam os padrões limnológicos de áreas não perturbadas e podem servir como futura referência para comparação com as propriedades dos sistemas aquáticos de áreas perturbadas, como as do Baixo Amazonas. Podem ser também utilizados como linha de base para estudos dos impactos antropogênicos e das mudanças climáticas sobre os ecossistemas aquáticos Amazônicos.

Abiotic variability among different aquatic systems of the central Amazon floodplain during drought and flood events

Abstract This paper examines water properties from lakes, (depression lakes, sensu Junk et al., 2012), channels (scroll lakes with high connectivity, sensu Junk et al., 2012) and paleo-channels (scroll lakes with low connectivity-sensu Junk et al., 2012, locally called ressacas) located in Mamirauá Sustainable Development Reserve, in Central Amazon floodplain, Amazonas, Brazil. We analysed surface temperature, conductivity, pH, dissolved oxygen, turbidity, transparency, suspended inorganic and organic matter, chlorophyll-a, pheophytin, total nitrogen, total phosphorus, organic and inorganic carbon in 2009 high water phase, 2009 and 2010 low water phases. Multivariate statistical analyses of 24 aquatic systems (6 ressacas, 12 lakes and 6 channels, 142 samples) were applied to the variables in order to: 1) quantify differences among aquatic system types; 2) assess how those differences are affected in the different phases of the hydrological year. First, we analysed the entire set of variables to test for differences among phases of the hydrological year and types of aquatic systems using a PERMANOVA two-way crossed design. The results showed that the all measured limnological variables are distinct regarding both factors: types of aquatic systems and hydrological phases. In general, the magnitude and amplitude of all variables were higher in the low water phase than in the high water phase, except for water transparency in all aquatic systems types. PERMANOVA showed that the differences between aquatic systems types and hydrological phases of all variables were highly significant for both main factors (type and phase) and for the type x phase interaction. Limnological patterns of Amazon floodplain aquatic systems are highly dynamic, dependent on the surrounding environment, flood pulse, main river input and system type. These patterns show how undisturbed systems respond to natural variability in such a diverse environment, and how distinct are those aquatic systems, especially during the low water phase. Aquatic systems in Mamirauá floodplain represent limnological patterns of almost undisturbed areas and can be used as future reference for comparison with disturbed areas, such as those of the Lower Amazon, and as a baseline for studies on the effects of anthropogenic influences and climate change and on Amazon aquatic ecosystem.

Resumo Esse trabalho investiga as propriedades da água de lagos (lagos de depressão, sensu Junk et al., 2012), canais (scroll lakes com alta conectividade, sensu Junk et al., 2012) e paleo canais (scroll lakes com baixa conectividade - sensu Junk et al., 2012, localmente chamados de ressaca) localizados na Reserva de Desenvolvimento Sustentável Mamirauá (RDSM), na planície de inundação da Amazônia Central, Amazonas, Brasil. Analisaram-se temperatura, condutividade, pH, oxigênio dissolvido, turbidez, e transparência da água na superfície e coletaram-se amostras de água na superfície para a determinação de material orgânico e inorgânico em suspensão, clorofila-a, feofitina, nitrogênio e fósforo total, carbono orgânico e inorgânico dissolvido, em duas fases da hidrógrafa, água alta em 2009, e água baixa em 2009 e 2010. Análises de estatística multivariada de 24 sistemas aquáticos (6 ressacas, 12 lagos e 6 canais, 142 amostras) foram realizadas para: 1) quantificar as diferenças entre os tipos de sistemas aquáticos; 2) determinar como essas diferenças são afetadas nas diferentes fases do ano hidrológico. Primeiramente foram analisadas todas as variáveis para testar as diferenças entre as fases do ano hidrológico e dos tipos de sistemas aquáticos utilizando o teste pareado cruzado PERMANOVA. Os resultados mostraram que todas as variáveis limnológicas medidas são distintas em relação a ambos os fatores: tipos de sistemas aquáticos e fases da hidrógrafa. Em geral, a magnitude e amplitude de todas as variáveis foram maiores na fase seca do que na cheia, com exceção da transparência da água em todos os tipos de sistemas aquáticos. Os resultados da PERMANOVA mostraram que as diferenças entre os tipos de sistemas aquáticos e as fases da hidrógrafa para todas as variáveis foram altamente significativas para ambos os fatores (tipo e fase) e ainda para a interação tipo x fase. Os padrões limnológicos dos sistemas aquáticos da planície de inundação Amazônica são altamente dinâmicos, dependente do ambiente ao redor, do pulso de inundação, do rio principal e do tipo de sistema. Os sistemas aquáticos da planície de inundação de Mamirauá representam os padrões limnológicos de áreas não perturbadas e podem servir como futura referência para comparação com as propriedades dos sistemas aquáticos de áreas perturbadas, como as do Baixo Amazonas. Podem ser também utilizados como linha de base para estudos dos impactos antropogênicos e das mudanças climáticas sobre os ecossistemas aquáticos Amazônicos.

Modeling pollution potential input from the drainage basin into Barra Bonita reservoir, São Paulo - Brazil.

In this study multi-criteria modeling tools are applied to map the spatial distribution of drainage basin potential to pollute Barra Bonita Reservoir, São Paulo State, Brasil. Barra Bonita Reservoir Basin had undergone intense land use/land cover changes in the last decades, including the fast conversion from pasture into sugarcane. In this respect, this study answers to the lack of information about the variables (criteria) which affect the pollution potential of the drainage basin by building a Geographic Information System which provides their spatial distribution at sub-basin level. The GIS was fed by several data (geomorphology, pedology, geology, drainage network and rainfall) provided by public agencies. Landsat satellite images provided land use/land cover map for 2002. Ratings and weights of each criterion defined by specialists supported the modeling process. The results showed a wide variability in the pollution potential of different sub-basins according to the application of different criterion. If only land use is analyzed, for instance, less than 50% of the basin is classified as highly threatening to water quality and include sub basins located near the reservoir, indicating the importance of protection areas at the margins. Despite the subjectivity involved in the weighing processes, the multi-criteria analysis model allowed the simulation of scenarios which support rational land use polices at sub-basin level regarding the protection of water resources.

Marshall's vein persistence: a rare and occasional finding during pacemaker implantation.

In adults the oblique vein of Marshall is usually absent or very thin, and it is hard to be found. In this case report we describe a case of persistence observed during pacemaker implantation.

Water quality changes in floodplain lakes due to the Amazon River flood pulse: Lago Grande de Curuaí (Pará).

Assurance of water quality for human consumption is essential for public health policies. In the Amazon floodplain, the seasonal water level variation causes periodic flooding of marginal areas that are usually used for settlements, agriculture and livestock. Therefore, the exchange of materials between the terrestrial and aquatic ecosystem affects the proportion of suspended and dissolved components in water and its physical-chemical characteristics, and consequently the quality of the water used by local people. Following this approach, the aim of this study is to evaluate changes in water quality in Lago Grande de Curuaí floodplain, Óbidos, Pará in response to the flood pulse, during one hydrological year from 2003 to 2004, based on water use classes (according to National Water Agency 357/2005 resolution) using chlorophyll-a and dissolved oxygen concentration as parameters and the eutrophication index. Ordinary kriging was applied to interpolate chlorophyll-a and dissolved oxygen and to predict values at non sampled locations. Each location was then classified according to water use acceptable parameters and to Carlson Trophic State Index modified by Toledo to map lake water classes and trophic status. The result showed that Lago Grande de Curuaí floodplain is a supereutrophic system, with levels of dissolved oxygen and chlorophyll-a not suitable for human supply during the receding water phase. These areas are located near the riverine communities, which can cause health problems due to the presence of potentially toxic algae. Therefore, monitoring water quality in Amazon lakes is essential to ensure the availability has appropriate quality for human and animal supplies.

Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential.

BACKGROUND AND AIMS: Mesenchymal stem cells from bone marrow (MSCs) may have the potential to differentiate in vitro and in vivo into hepatocytes. We investigated whether transplanted human MSCs (hMSCs) may engraft the liver of non-obese diabetic severe combined immuno-deficient (NOD/SCID) mice and differentiate into cells of hepatic lineage. METHODS: Ex vivo expanded, highly purified and functionally active hMSCs from bone marrow were transplanted (caudal vein) in sublethally irradiated NOD/SCID mice that were either exposed or not to acute liver injury or submitted to a protocol of chronic injury (single or chronic intraperitoneal injection of CCl(4), respectively). Chimeric livers were analysed for expression of human transcripts and antigens. RESULTS: Liver engraftment of cells of human origin was very low in normal and acutely injured NOD/SCID mice with significantly higher numbers found in chronically injured livers. However, hepatocellular differentiation was relatively rare, limited to a low number of cells (ranging from less than 0.1% to 0.23%) as confirmed by very low or not detectable levels of human transcripts for alpha-fetoprotein, CK18, CK19 and albumin in either normal or injured livers. Finally, a significant number of cells of human origin exhibited a myofibroblast-like morphology. CONCLUSIONS: Transplanted hMSCs have the potential to migrate into normal and injured liver parenchyma, particularly under conditions of chronic injury, but differentiation into hepatocyte-like cells is a rare event and pro-fibrogenic potential of hMSC transplant should be not under-evaluated.

Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans.

BACKGROUND AND AIMS: Myofibroblast-like cells, originating from activation of hepatic stellate cells (HSC/MFs), play a key role in liver fibrosis, a potentially reversible process that may rely on induction of HSC/MFs apoptosis. While this possibility has been shown in cultured rat HSC, very limited data are currently available for human HSC/MFs. METHODS: Cultured human HSC/MFs were exposed to several proapoptotic stimuli, including those known to induce apoptosis in rat HSC/MFs, and induction of cell death and related mechanisms were investigated using morphology, molecular biology, and biochemical techniques. RESULTS: In this study we report that fully activated human HSC/MFs did not undergo spontaneous apoptosis and survived to prolonged serum deprivation, Fas activation, or exposure to nerve growth factor, tumour necrosis factor alpha (TNF-alpha), oxidative stress mediators, doxorubicin, and etoposide. Induction of caspase dependent, mitochondria driven apoptosis in HSC/MFs was observed only when protein synthesis or transcription were inhibited. Importantly, the process of HSC activation was accompanied by changes in expression of a set of genes involved in apoptosis control. In particular, activated human HSC/MFs in culture overexpressed Bcl-2. The role of Bcl-2 was crucial as Bcl-2 silenced cells became susceptible to TNF-alpha induced apoptosis. Finally, Bcl-2 was markedly expressed in HSC/MFs present in liver tissue obtained from patients with hepatitis C virus related cirrhosis. CONCLUSIONS: Human activated HSC/MFs are resistant to most proapoptotic stimuli due to Bcl-2 overexpression and this feature may play a key role in the progression of fibrosis in chronic liver diseases.

Dose dependent and divergent effects of superoxide anion on cell death, proliferation, and migration of activated human hepatic stellate cells.

BACKGROUND AND AIMS: Activated myofibroblast-like cells, originating from hepatic stellate cells (HSC/MFs) or other cellular sources, play a key profibrogenic role in chronic liver diseases (CLDs) that, as suggested by studies in animal models or rat HSC/MFs, may be modulated by reactive oxygen intermediates (ROI). In this study, human HSC/MFs, exposed to different levels of superoxide anion (O(2)(.-)) and, for comparison, hydrogen peroxide (H(2)O(2)), were analysed in terms of cytotoxicity, proliferative response, and migration. METHODS: Cultured human HSC/MFs were exposed to controlled O(2)(.-) generation by hypoxanthine/xanthine oxidase systems or to a range of H(2)O(2) concentrations. Induction of cell death, proliferation, and migration were investigated using morphology, molecular biology, and biochemical techniques. RESULTS: Human HSC/MFs were shown to be extremely resistant to induction of cell death by O(2)(.-) and only high rates of O(2)(.-) generation induced either necrotic or apoptotic cell death. Non-cytotoxic low levels of O(2)(.-), able to upregulate procollagen type I expression (but not tissue inhibitor of metalloproteinase 1 and 2), stimulated migration of human HSC/MFs in a Ras/extracellular regulated kinase (ERK) dependent, antioxidant sensitive way, without affecting basal or platelet derived growth factor (PDGF) stimulated cell proliferation. Non-cytotoxic levels of H(2)O(2) did not affect Ras/ERK or proliferative response. A high rate of O(2)(.-) generation or elevated levels of H(2)O(2 )induced cytoskeletal alterations, block in motility, and inhibition of PDGF dependent DNA synthesis. CONCLUSIONS: Low non-cytotoxic levels of extracellularly generated O(2)(.-) may stimulate selected profibrogenic responses in human HSC/MFs without affecting proliferation.

Tratamiento tópico sobre úlceras varicosas de evolución tórpida con ampollas monodosis estériles de ciprofloxacino.La efectividad frente a suero fisiológico / Effectiveness of topical treatment of chronic varicose ulcers with sterile single-dose ciprofloxacin ampoules versus physiologic serum

OBJETIVO: Determinar la efectividad de la aplicación de solución tópica estéril de ciprofloxacino y suero fisiológico como tratamiento local en úlceras de etiología venosa, frente al empleo de suero fisiológico exclusivamente. DISEÑO: Estudio seudoexperimental cruzado. MATERIAL Y MÉTODO: Estudio cruzado, en donde se incluyeron pacientes con lesiones varicosas de más de tres semanas de evolución (n = 63), con una media de edad de 76,3 ñ 16,8 años, 21 varones (33 por ciento; 69,9 ñ 19,9 años) y 42 mujeres (67 por ciento; 80,2 ñ 12,3 años). La misma muestra fue distribuida para el análisis en dos grupos de pacientes; grupo A (N = 63), en el que se realizó una cura semioclusiva húmeda con ciprofloxacino (solución de cloruro sódico al 0,9 por ciento aplicada a chorro con jeringuilla de 20 ml y aguja desechable) junto con gasas (3-4 por acto) de entramado con algodón, ampollas monodosis estériles desechables de ciprofloxacino (n = 63), y grupo B, en el que se aplicó suero fisiológico sin ampollas monodosis (n = 63), utilizado durante un máximo de 2 semanas. RESULTADOS: En el estudio cruzado la respuesta fue positiva en 29 pacientes pertenecientes al grupo B y en 41 del grupo A (el 65 frente al 46 por ciento; p = 0,000). La disminución porcentual de la superficie fue del 31,2 frente al 9,3 por ciento (1,46 frente a 0,47 cm2; p = 0,00) en los grupos A y B, respectivamente. Los resultados de los cultivos para el estudio cruzado fueron: 37,5 por ciento Pseudomonas, 17,6 por ciento informado como estéril, 17,1 por ciento con Streptococcus grupo D, 14,1 por ciento como flora saprofita. CONCLUSIONES: El tratamiento con ciprofloxacino tópico sobre las lesiones varicosas de larga evolución junto al suero fisiológico parece ofrecer mejores porcentajes de respuesta inicial respecto al uso de suero fisiológico exclusivamente. La presencia de fibrina previa al tratamiento con suero no parece modificar la respuesta posterior al mismo. Añadir ciprofloxacino tópico en lesiones sin fibrina favorece la mejoría de la respuesta frente al uso únicamente de suero fisiológico. (AU)

Effect of chronic manganese treatment on adenosine tissue levels and adenosine A2a receptor binding in diverse regions of mouse brain.

In the present study the effects of chronic manganese (Mn) treatment on adenosine A2a receptor binding in mouse brain have been assessed. Male albino mice were divided in two groups: In the Mn-treated group, the animals were injected intraperitoneally (i.p.) with MnCl2 (5 mg/kg/day) five days per week during 9 weeks; in the control group, they were injected likewise with a saline solution. A significant decrease of the Kd without alteration of Bmax in the cerebellum and, an increase of the Kd and Bmax in hippocampus of mice treated with Mn were found. Also, an increase of Kd in frontal cortex was observed. The binding parameters in caudate nucleus, olfactory bulb and hypothalamus were not altered by Mn. A significant decrease in the adenosine concentration in caudate nucleus, olfactory bulb and hypothalamus, without significant changes in hippocampus, frontal cortex and cerebellum was also detected. These findings suggest that chronic administration of Mn could affect adenosine receptor function and turnover, depending on the brain region analyzed.

White blood cell count and insulin resistance in patients with coronary artery disease.

White blood cell (WBC) count has been shown as a risk factor for cardiovascular disease. Decreased insulin sensitivity has been suggested as the link between these two entities. Our aim was to study the potential relation between insulin sensitivity and WBC count in patients with coronary artery disease. In order to assess insulin sensitivity, we performed 83 insulin suppression tests before and after therapy in 50 patients with coronary artery disease. Patients with glucose intolerance, arterial hypertension or obesity were excluded. Steady-state plasma glucose (SSPG) and insulin sensitivity index (ISI=1 000 x glucose infusion rate/SSPG) were considered as a measure of insulin sensitivity. WBC count, blood platelets, fibrinogen, microalbuminuria, creatinine, urea and HbA1c were also assessed. Simple and multiple correlation analysis were carried out between insulin sensitivity parameters and the other variables measured. There were significant correlation between SSPG and WBC count (r=0,32: p=0,003) and microalbuminuria (r=0,28: p=0,012). We also found statistically significant correlation between ISI and WBC count (r=0,27: p=0,015) and microalbuminuria (r=0,24: p=0,029). No correlation could be detected between either SSPG or ISI and the other variables measured. In multiple regression analysis, WBC count was found to be an independent predictor of both SSPG (p<0.01) and ISI (p<0.05). Our data show the existence of a significant relationship between decreased insulin sensitivity and WBC count in patients with coronary artery disease. The results of this study suggest that an elevated WBC count could be postulated as part of the insulin resistant syndrome.

Disfunción eréctil, viagra y riesgo cardiovascular / Erectile dysfunction, "viagra" and cardiovascular risk

La disfunción eréctil (DE) comparte mecanismos fisiopatológicos comunes con la enfermedad cardíaca isquémica y puede ser considerada en sí misma un factor de riesgo cardiovascular. El riesgo de muerte u otros eventos coronarios se incrementa significativamente en pacientes que la padecen. La frecuencia de muerte súbita en relación con la actividad sexual es del 2,5 por ciento, aumentando con la edad y la relación extramarital. Estos hechos obligan a pensar en los potenciales efectos de la prescripción de Viagra en pacientes sedentarios con actividad sexual muy reducida y edad avanzada, lo que resulta de gran preocupación, incluso para la opinión pública. En general, se considera que la ergometría puede simular el estrés originado durante la relación sexual y ser un buen elemento para marcar la población en riesgo. Aunque los estudios clínicos realizados con sildenafilo muestran relativamente pocos efectos adversos cardiovasculares, estos estudios excluyeron pacientes con insuficiencia cardíaca, infarto de miocardio o accidente cerebrovascular en los últimos 6 meses. Por tanto, los pacientes cardiópatas incluidos sólo representan una pequeña porción de los que pueden tomar sildenafilo en la práctica real. Este trabajo repasa de una forma práctica las contraindicaciones absolutas y relativas de la toma de sildenafilo. Se presentan también las recomendaciones para su uso en situaciones de riesgo, así como el manejo del cuadro coronario en un paciente que ha tomado Viagra. (AU)

Erythrogenic toxin type B and its precursor isolated from nephritogenic streptococci induce leukocyte infiltration in normal rat kidneys.

BACKGROUND: Leukocyte infiltration is a common feature in renal biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). Cationic streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) have been implicated in the pathogenesis of the disease, and the presence of ETB has been evidenced in renal biopsies from patients with APSGN. The present studies were performed to determine the effect of the ETBP and ETB on renal leukocyte infiltration and the mechanism(s) implicated in the phenomenon. METHODS: Male Sprague-Dawley rats were injected intrarenally with 100 microg of ETB or ETBP. Animals were sacrificed at 1, 6 and 24 h after injection and renal samples were studied by indirect immunofluorescence for the presence of leukocyte common antigen (LCA+) cells, C3, monocyte chemotactic protein-1 (MCP-1) and intercellular adhesion molecule-(ICAM-1), and by direct immunofluorescence for the presence of immunoglobulins. ETB and ETBP were tested for chemotactic effect and migration inhibition factor (MIF) activity by chemotaxis under agarose and agarose microdroplet methods, respectively. Streptococcal proteins were also tested for the capacity to induce MIF activity in rat glomerular cultures. To test for the influence of cationic charge on renal LCA+ cell infiltration, rats were injected with cationized ferritin or polyethyleneimine (PEI) and sacrificed 1 h later. RESULTS: An increased number of LCA+ cells was found in glomeruli and interstitial areas in ETB- or ETBP-injected animals. ETB and ETBP showed chemotactic and MIF activity on neutrophils and macrophages, and ETBP induced MIF activity in supernatants of glomerular cultures. Data obtained from C3, MCP-1, ICAM-1 or immunoglobulin renal staining in experimental animals were not significantly different when compared to control values. Cationized compounds failed to induce LCA+ cell infiltration; however, an increased number of glomerular LCA+ cells was observed after PEI perfusion. CONCLUSIONS: ETB and ETBP induce renal LCA+ cell infiltration during a short period after intrarenal injection, and this finding could be mediated by chemotactic and MIF activities. These observations could be relevant in the early events of pathogenesis of APSGN.

Evolution of insulin resistance in coronary artery disease patients on four different pharmacological therapies.

The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) x 10(3). A second insulin suppression test was performed after 6 months' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients. There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.