Ambulatory blood pressure and physical activity in heart failure

Background. Ambulatory blood pressure (ABP) measurement is a means of monitoring cardiac function in a noninvasive way, but little is known about ABP in heart failure (HF) patients. Blood pressure (BP) declines during sleep as protection from consistent BP load, a phenomenon termed "dipping." The aims of this study were (1) to compare BP dipping and physical activity between two groups of HF patients with different functional statuses and (2) to determine whether the strength of the association between ambulatory BP and PA is different between these two different functional statuses of HF. ^ Methods. This observational study used repeated measures of ABP and PA over a 24-hour period to investigate the profiles of BP and PA in community-based individuals with HF. ABP was measured every 30 minutes by using a SpaceLabs 90207, and a Basic Motionlogger actigraph was used to measure PA minute by minute. Fifty-six participants completed both BP and physical activity for a 24-hour monitoring period. Functional status was based on New York Heart Association (NYHA) ratings. There were 27 patients with no limitation of PA (NYHA class I HF) and 29 with some limitation of PA but no discomfort at rest (NYHA class II or III HF). The sample consisted of 26 men and 30 women, aged 45 to 91 years (66.96 ± 12.35). ^ Results. Patients with NYHA class I HF had significantly greater dipping percent than those with NYHA class II/III HF after controlling their left ventricular ejection fraction (LVEF). In a mixed model analysis (PROC MIXED, SAS Institute, v 9.1), PA was significantly related to ambulatory systolic and diastolic BP and mean arterial pressure. The strength of the association between PA and ABP readings was not significantly different for the two groups of patients. ^ Conclusions. These preliminary findings demonstrate differences between NYHA class I and class II/III of HF in BP dipping status and ABP but not PA. Longitudinal research is recommended to improve understanding of the influence of disease progression on changes in 24-hour physical activity and BP profiles of this patient population. ^ Key Words. Ambulatory Blood Pressure; Blood Pressure Dipping; Heart Failure; Physical Activity. ^

Role of activation of the protein tyrosine kinase, Src, in colorectal cancer chemoresistance

Advances in therapy for colorectal cancer have been hampered by development of resistance to chemotherapy. The Src family of protein tyrosine kinases has been associated with colorectal cancer development and progression. Activation of the prototypic member of the family, Src, occurs in advanced colorectal cancer and is associated with a worse outcome. This work tests the hypotheses that Src activation contributes to chemoresistance in some colon tumors and that this resistance can be overcome by use of Src inhibitors. The aims of the proposal were to (1) determine if constitutive Src activation is sufficient to induce oxaliplatin resistance; (2) evaluate the role of reactive oxygen species (ROS) in the activation of Src after oxaliplatin treatment; (3) determine the frequency of Src activation in liver metastases after oxaliplatin treatment; and (4) evaluate the safety, preliminary efficacy, and pharmacodynamics of the combination of dasatinib with oxaliplatin-based therapy in patients with metastatic colorectal cancer. ^ Using a panel of colon cancer cell lines and murine models, I demonstrate that administration of oxaliplatin, a commonly utilized chemotherapy for colorectal cancer, results in an increased activation of Src. The activation occurs acutely in some, but not all, colorectal carcinoma cell lines. Cell lines selected for oxaliplatin resistance are further increased in Src activity. Treatment of cell lines with dasatinib, a non-selective pharmacologic inhibitor of the Src family kinases synergistically killed some, but not all cell lines. Cell lines with the highest acute activation of Src after oxaliplatin administration were the most sensitive to the combination therapy. Previous work demonstrated that siRNA to Src increased sensitivity to oxaliplatin, suggesting that the effects of dasatinib are primarily due to its ability to inhibit Src in these cell lines. ^ To examine the mechanism underlying these results, I examined the effects of reactive oxygen species (ROS), as previous studies have demonstrated that platinum chemotherapeutics result in intracellular oxidative stress. I demonstrated that oxaliplatin-induced reactive oxygen species were higher in the cell lines with Src activation, relative to those in which Src was not activated. This oxaliplatin-induced Src activation was blocked by the administration of anti-oxidants, thereby demonstrating that synergistic killing between dasatinib and oxaliplatin was associated with the ability of the latter to generate ROS. ^ In a murine model of colorectal cancer metastasis to the liver, the combination of dasatinib and oxaliplatin was more effective in reducing tumor volume than either agent alone. However, when oxaliplatin resistant cell lines were treated with a combination of oxaliplatin and AZD0530, an inhibitor in the clinic with increased specificity for Src, no additional benefit was seen, although Src was activated by oxaliplatin and Src substrates were inhibited. The indolent growth of oxaliplatin-resistant cells, unlike the growth of oxaliplatin resistant tumors in patients, precludes definitive interpretation of these results. ^ To further explore Src activation in patients with oxaliplatin exposure and resistance, an immunohistochemistry analysis of tumor tissue from resected liver metastases of colorectal cancer was performed. Utilizing a tissue microarray, staining for phosphorylated Src and FAK demonstrated strong staining of tumor relative to stromal and normal liver. In patients recently exposed to oxaliplatin, there was increased FAK activation, supporting the clinical relevance of the prior preclinical studies. ^ To pursue the potential clinical benefit of the combination of Src inhibition with oxaliplatin, a phase IB clinical trial was completed. Thirty patients with refractory metastatic colorectal cancer were treated with a combination of 5-FU, oxaliplatin, an epidermal-growth factor receptor monoclonal antibody, and dasatinib. The recommended phase II dose of dasatinib was established, and toxicities were quantified. Pharmacodynamic studies demonstrated increased phosphorylation of the Src substrate paxillin after dasatinib therapy. Tumor biopsies were obtained and Src expression levels were quantitated. Clinical benefit was seen with the combination, including a response rate of 20% and disease control rate of 56%, prompting a larger clinical study. ^ In summary, although Src is constitutively activated in metastatic colorectal cancer, administration of oxaliplatin chemotherapy can further increase its activity, through a reactive oxygen species dependent manner. Inhibition of Src in combination with oxaliplatin provides additional benefit in vitro, in preclinical animal models, and in the clinic. Further study of Src inhibition in the clinic and identification of predictive biomarkers of response will be required to further advance this promising therapeutic target. ^

Producción de maíz bajo diferentes regímenes de riego complementario en Río Cuarto, Córdoba, Argentina. II. Producción de materia seca

El objetivo de este trabajo fue evaluar el efecto del riego complementario sobre el rendimiento de materia seca del cultivo de maíz. Se usó un diseño completamente al azar con 5 tratamientos y 4 repeticiones. Para efectuar la programación de los diferentes tratamientos de riego se dividió el ciclo del cultivo en tres etapas (precrítico, crítico y poscrítico). Para la determinación del momento de riego se realizó un balance hídrico con datos climáticos obtenidos de la Estación Meteorológica ubicada en el lugar del ensayo. El riego se efectuó con un equipo presurizado de avance lateral. El maíz cumplió su ciclo en 138 días en todos los tratamientos y requirió 1660,6 grados día para alcanzar madurez fisiológica. El rendimiento de materia seca tuvo diferencias significativas (a = 0,05) entre los distintos tratamientos regados y entre éstos y el testigo. Los valores extremos de producción fueron de 34.628 kg.ha-1 en el tratamiento 1 y 20.414 kg.ha-1 en el tratamiento sin riego. La cantidad de agua aplicada varió entre 360 y 300 mm y el agua total consumida en el ciclo del cultivo, según el balance hídrico, fue para los tratamientos con riego de 575 mm ± 15 mm y para el testigo sin riego de 308 mm. La eficiencia de uso de agua para materia seca tuvo diferencias significativas (a = 0,05) entre los tratamientos regados (5,7 kg.m-3) y no regados (6,6 kg.m-3). El índice de cosecha fue de 0,49.

Comentarios y conclusiones II Seminario Internacional : la interdisciplina en el ordenamiento territorial

Por el éxito y trascendencia de sus eventos anteriores, el Instituto CIFOT siente la obligación de hacer conocer las principales conclusiones del II Seminario de Ordenamiento Territorial, el que comienza a marcar pautas a partir de las preocupaciones comunes, enfoques teórico-metodológicos prevalecientes en el Ordenamiento Territorial, la planificación Estratégica y Ambiental, como también sobre las prácticas de gestión de la información territorial. Se sintetiza la idea central de las conferencias Magistrales: - Dr. Juan Gastó- Pontificia Universidad Católica de Chile- presenta “ La Ordenación Territorial como eje del Desarrollo Rural", cuyo punto central es la imposibilidad de separar la problemática territorial urbana de la rural. - Dr. Eduardo Salinas- Universidad de La Habana , Cuba- en “El Ordenamiento Territorial como instrumento de la Planificación y Gestión Ambiental" establece la necesidad de una planificación sustentable ambientalmente, con una concepción sistémica y holística de los problemas. -Dra. Elsa Laurelli -Universidad de La Plata , Argentina- en “Nuevas Tendencias del Ordenamiento Territorial en una Economía de Mercado. Limitaciones y posibilidades" plantea coexistencia de áreas receptoras de IDE vs espacios degradados y con problemáticas sociales y reflexiona sobre el rol del Estado para atenuar los efectos del mercado en el territorio y la sociedad. - Dr. Pablo Ciccolella -UBA-, Argentina. En “ Desafíos y opciones en la Gestión Urbana bajo el Capitalismo Global: Planificación Estratégica y Desarrollo Económico-Territorial" alerta sobre la planificación llave en mano que genera un desarrollo elitista, banal y efímero. - Dr. Mariano Zamorano -Universidad Nacional de Cuyo, Mendoza- presenta “ Una propuesta de Regionalización de la Provincia de Mendoza sobre la base de la Lógica Territorial " destinada a optimizar la gestión municipal y provincial. Al II Seminario de Ordenamiento Territorial concurren alrededor de 140 personas y se exponen 43 trabajos en las siguientes áreas temáticas : - 1 Nuevas tendencias en el Ordenamiento territorial . - 2 Ambiente y Ordenamiento Territorial. - 3 El Ordenamiento Territorial en el ámbito urbano. - 4 El Ordenamiento Territorial en el ámbito rural. - 5 La gestión de la información en el Ordenamiento Territorial. - 6 El rol de las Instituciones en el Ordenamiento Territorial. Conclusiones De l rico debate e intercambio de ideas realizado durante el II Seminario, se extraen tres grandes temas: - La necesidad de una visión general y holística del territorio, evitando la fragmentación disciplinar. - La interdisciplina, como campo de convergencia de problemáticas complejas. La planificación estratégica como instancia participativa y visión integral del territorio. - La metodología para el Ordenamiento Territorial debe ser verdaderamente aplicada. No se puede seguir planificando con una racionalidad limitada en busca de una imagen objetivo rígida mientras el territorio, conformado por sistemas complejos y abiertos, está en constante cambio por exigencias propias de lo global. - Un Estado en retirada no contiene la estructura necesaria ni el consenso para imponerse en sociedades democráticas con dominio absoluto de tipo capitalista.