Evaluación del impacto de la participación comunitaria en la vigilancia de Chagas / Evaluation of the impact of community participation in the surveillance of Chagas

El objetivo del presente estudio es efectuar el análisis del impacto de la vigilancia en sus diferentes modalidades en el control de la infección por T. cruzi y la densidad vectorial (Triatoma infestans). Material y métodos: El trabajo fue desarrollado en el Departamento de Capayán, en la provincia de Catamarca, Argentina. Se seleccionaron aleatoriamente 5 comunidades rurales y 3 comunidades peri-urbanas para desarrollar el estudio. Indicadores utilizados: a) infestación domiciliaria en los meses 24, 48 y 96; y b) Infección por T.cruzi de menores de 14 años. Resultados: Se observa persistencia de triatomineos durante el periodo de seguimiento y cuando se comparan los datos del estudio de base (2007) con los obtenidos en el año 2009 y 2012 existe significancia estadística (p <0.04) entre áreas. Se capturaron 1.89 insectos/intradomicilio en áreas con vigilancia activa versus 5.21 insectos/intradomicilio en áreas donde la misma no existió. Se demuestra la existencia de infecciones recientes en niños menores de 4 años e hijos de mujeres negativas para T. cruzi en áreas sin vigilancia activa (3 niños). Conclusión: En la presente investigación se demuestra el impacto de la vigilancia activa en sus diferentes modalidades por la no existencia de casos nuevos vectoriales en el período de seguimiento. (AU)

The aim of this study is to perform the analysis of the impact of surveillance in its various forms in the control of infection by T. cruzi and vector density (Triatoma infestans). Material and Methods: The work was developed in the Department of Capayán, in the Province of Catamarca, Argentina. Eight rural communities were selected to develop the study. Indicators used: a) house infestation in 24 months, 48 and 96; b) T. cruzi infection in children under 14 years. Results: Persistence of triatomine It is observed during the monitoring period as the baseline study (2007) thus obtained in 2009 compared to 2012 there is statistical significance (p <0.04) between areas. 1.89 insect / intradomicile were captured in areas with active surveillance versus 5.21 insect/intradomicile in areas where it did not exist. The existence of recent infections in children under four years of negative women and children for T. cruzi in areas without active surveillance (3 children) is demonstrated. Conclusion: In this research, the impact of active surveillance in its various forms by Vector exists no new cases in the follow-up period shown. (AU)

Parathyroid hormone-related protein promotes quiescence and survival of serum-deprived chondrocytes by inhibiting rRNA synthesis.

Parathyroid hormone-related protein (PTHrP) was initially recognized for its ability to promote parathyroid hormone-like bioactivity in kidney, bone, and squamous epithelial cells. PTHrP is a multifunctional protein in which bioactivity is mediated by two distinct pathways. Its classic parathyroid hormone-like activity results from binding of its amino terminus to cell surface PTH1R and activation of signal transduction pathways. Another less well recognized pathway involves translocation of PTHrP to the nucleus via a mid-region bipartite nuclear targeting sequence (NTS), similar in structure and function to those found in retroviral regulatory proteins. PTHrP was identified in the nucleus of several different cell types in vivo and in vitro, where it has been implicated in cell cycle progression, cellular differentiation, and apoptosis. In previous work we showed that nuclear translocation of PTHrP enhanced the survival of serum-deprived chondrogenic cells, associated with RNA, and localized to a region of the nucleus rich in complexes of newly transcribed ribosomal RNA and protein. In this work we have used two chondrogenic cell lines, CFK2 (PTH1R+) and 27m21 (PTH1R-) to further explore mechanisms whereby PTHrP rescues immature chondrocytes from apoptosis. Endogenous PTHrP and exogenous PTHrP NTS peptide protected serum-deprived cells from apoptosis, in the presence and absence of PTH1R. The survival of cells expressing PTHrP and those treated with PTHrP NTS peptide was associated with a rapid shift into G(o)/G1 accompanied by a significant down-regulation of rRNA synthesis and a decrease in the number of actively translating polyribosome complexes. Together with our previous observations, this work predicts a role for PTHrP in modulating ribosome biogenesis and preventing chondrogenic cells from progressing through the cell cycle in an unfavorable environment.

Alterations in the sensing and transport of phosphate and calcium by differentiating chondrocytes.

During endochondral bone formation and fracture healing, cells committed to chondrogenesis undergo a temporally restricted program of differentiation that is characterized by sequential changes in their phenotype and gene expression. This results in the manufacture, remodeling, and mineralization of a cartilage template on which bone is laid down. Articular chondrocytes undergo a similar but restricted differentiation program that does not proceed to mineralization, except in pathologic conditions such as osteoarthritis. The pathogenesis of disorders of cartilage development and metabolism, including osteochondrodysplasia, fracture non-union, and osteoarthritis remain poorly defined. We used the CFK2 model to examine the potential roles of phosphate and calcium ions in the regulatory pathways that mediate chondrogenesis and cartilage maturation. Differentiation was monitored over a 4-week period using a combination of morphological, biochemical, and molecular markers that have been characterized in vivo and in vitro. CFK2 cells expressed the type III sodium-dependent phosphate transporters Glvr-1 and Ram-1, as well as a calcium-sensing mechanism. Regulated expression and activity of Glvr-1 by extracellular phosphate and parathyroid hormone-related protein was restricted to an early stage of CFK2 differentiation, as evidenced by expression of type II collagen, proteoglycan, and Ihh. On the other hand, regulated expression and activity of a calcium-sensing receptor by extracellular calcium was most evident after 2 weeks of differentiation, concomitant with an increase in type X collagen expression, alkaline phosphatase activity and parathyroid hormone/parathyroid hormone-related protein receptor expression. On the basis of these temporally restricted changes in the sensing and transport of phosphate and calcium, we predict that extracellular phosphate plays a role in the commitment of chondrogenic cells to differentiation, whereas extracellular calcium plays a role at a later stage in their differentiation program.