Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease

Patients with Parkinson's disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S-associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated PD.This work was supported by the grant PI11/00228 from Instituto de Salud Carlos III.Peer Reviewe

Visiones de fin de siglo

La presente publicación concentra los trabajos presentados por investigadores nacionales y extranjeros en el "Il Encuentro Internacional de Historia. El siglo XX en Bolivia y América Latina. Visiones de fin de siglo", que se realizó en la ciudad de Cochabamba entre el 27 y el 31 de julio de 1998. El encuentro fue organizado por la "Coordinadora de Historia. Investigadores Asociados" y contó con el auspicio del Centro Cultural Portales con sede en esa ciudad, así como con el apoyo de las siguientes instituciones: Facultad de Humanidades de la Universidad Mayor de San Andrés de La Paz, Plural Editores, Anden Silver Corporation, Embajada de México, Lloyl Aéreo Boliviano, Compañía Industrial de Tabacos S.A., Banco Mercantil y La Estrella. La Coordinadora de Historia, que reúne a más de 20 historiadores/as bolivianos/as, desarrolló en 1994 un encuentro similar sobre el siglo XIX en la ciudad de Sucre. Las actas del mismo, al que asistieron renombrados historiadores de Europa, Estados Unidos, Latinoamérica y Bolivia, ya han sido publicadas. En esta oportunidad, 48 expositores abordaron las siguientes temáticas planteadas por los organizadores del Congreso: - Archivos documentales bolivianos del siglo XX. - Proyectos y modelos de sociedad en Bolivia. - Estructuras y practicas políticas en Bolivia y America Latina. - Proyectos, estructuras y modelos económicos en Bolivia y América Latina. - Movimientos, actores y estructuras sociales en Bolivia y America Latina. - Culturas hegemónicas y contraculturas en Bolivia y America Latina. Diez de ellos, Horacio Cerruti, Francisco Zapata, Antonio García de Léon, Antonio Mitre, Melvin Burke, H.C.F, Mansilla, Janvier Sanjinés, Jorge Lazarte, René Antonio Mayorga y Gonzalo Sánchez de Lozada, estuvieron encargados de desarrollar "ponencias magistrales", las que se caracterizaron por intentar visiones más globales o de síntesis sobre las temáticas generales trabajadas en cada una de las jornadas. El encuentro sobre el siglo XX, tuvo la particularidad de reunir a especialistas nacionales extranjeros de distintas disciplinas de las ciencias sociales y humanas como historiadores, sociólogos, antropólogos, economistas y literatos, con el objetivo de lograr el intercambio de visiones y perspectivas de análisis bajo una óptica multirdisciplinaria. Ello permitió romper barreras entre las disciplinas que muchas veces son resultado de prejuicos y celos y desarrollar un rico y creativo débale que muy pocas yeces se realiza en nuestro medio

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd