Megaproyectos urbanos y productivos. Impactos socio-territoriales

El desarrollo de megaproyectos productivos trae consigo oportunidades para el crecimiento económico, la generación de empleos y el desarrollo regional. No obstante, en la actualidad, los grandes temas como la expansión urbana, el desarrollo industrial, las cementeras, la minería, el uso intensivo del agua y demás recursos naturales, preocupan a las comunidades por los impactos generados y porque en lo general, no consideran la racionalidad y responsabilidad ambiental y social hacia el entorno. En este contexto son diversos los estudios científicos que, en el marco de la política de económica imperante, intentan posicionarse como alternativas a proyectos económicos que confrontan los intereses particulares y comunitarios y que afectan la salud humana y ambiental. Megaproyectos urbanos y productivos. Impactos socio-territoriales, reúne veinticinco textos académicos sobre las afectaciones que éstos emprendimientos tienen para la sociedad y el entorno. Los temas expuestos recogen experiencias en el desarrollo urbano, industrial, turístico, portuario y aeroportuario, entre otros. Así mismo se retoman temas como la ética, la dialéctica, la política y la economía y su relación en el emprendimiento de megaproyectos. La búsqueda de esquemas productivos racionales y responsables con el entorno, que reivindiquen el derecho de las comunidades a un medio ambiente sano, a la preservación del territorio y sus recursos y de las formas de vida tradicionales, son los referentes para la realización del presente libro. Como elemento central se concibe el territorio como contenedor de identidad y vida, siendo preocupación y tema de estudio de la comunidad académica, las organizaciones de la sociedad civil y las redes de activistas organizados.UAEM, CONACyT, se

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass

Inflammatory and pro-resolving lipids in trypanosomatid infections: A key to understanding parasite control

© 2018 López-Muñoz, Molina-Berríos, Campos-Estrada, Abarca-Sanhueza, Urrutia-Llancaqueo, Peña-Espinoza and Maya. Pathogenic trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp.) are protozoan parasites that cause neglected diseases affecting millions of people in Africa, Asia, and the Americas. In the process of infection, trypanosomatids evade and survive the immune system attack, which can lead to a chronic inflammatory state that induces cumulative damage, often killing the host in the long term. The immune mediators involved in this process are not entirely understood. Most of the research on the immunologic control of protozoan infections has been focused on acute inflammation. Nevertheless, when this process is not terminated adequately, permanent damage to the inflamed tissue may ensue. Recently, a second process, called resolution of inflammation, has been proposed to be a pivotal process in the control of parasite burden and establishment of chronic inf

Effect of statins on inflammation and cardiac function in patients with chronic Chagas disease: A protocol for pathophysiological studies in a multicenter, placebo-controlled, proof-of-concept phase II trial.

BackgroundCardiac complications, including heart failure and arrhythmias, are the leading causes of disability and death in Chagas disease (CD). CD, caused by the Trypanosoma cruzi parasite, afflicts 7 million people in Latin America, and its incidence is increasing in non-endemic countries due to migration. The cardiac involvement is explained by parasite-dependent, immune-mediated myocardial injury, microvascular abnormalities, and ischemia. Current treatment of early CD includes the administration of nifurtimox and benznidazole. However, their efficacy is low in the chronic phase and may induce severe adverse events, forcing therapy to halt. Therefore, finding innovative approaches to treat this life-threatening tropical disease is of utmost importance. Thus, improving the efficacy of the current antichagasic drugs by modifying the inflammatory response would render the current treatment more effective. It has been reported that, in mice, simvastatin decreases cardiac inflammation and endothelial activation, and improves cardiac function, effects that require clinical confirmation.ObjectiveThe study aims to analyze whether two doses of Atorvastatin, administered after CD treatment is completed, are safe and more efficacious than the antiparasitic drugs alone in reducing general inflammation and improving endothelial and cardiac functions in a proof-of-concept, placebo-controlled phase II trial.Methods300 subjects will be recruited from four Chilean hospitals with an active Program for the Control of Chagas Disease. 40 or 80 mg/day of atorvastatin or placebo will be administered after completion of the antichagasic therapy. The patients will be followed up for 12 months. Efficacy will be determined by measuring changes in plasma levels of anti-inflammatory and pro-inflammatory cytokines, soluble cell adhesion molecules, BNP, and cTnT. Also, the resting 12-lead ECG and a 2D-echocardiogram will be obtained to evaluate cardiac function.Trial registrationClinicalTrials.gov Identifier: NCT04984616

Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target

Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC50 of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in infected BALB/c mice, pentamidine failed to get synergy with benznidazole, measured on mice survival, parasitemia and amastigote nest quantification. To further explain the in vitro antagonism, we explored whether pentamidine affects intracellular trypanothione levels, however, pentamidine produced no change in trypanothione concentrations. Finally, the T cruzi polyamine permease (TcPAT12) was overexpressed in epimastigotes, showing that pentamidine has the same trypanocidal effect, independently of transporter expression levels. These results suggest that, in spite of the high potency in the putrescine transport blockade, TcPAT12 permease is not the main target of pentamidine, and could explain the lack of synergism between pentamidine and benznidazole. (C) 2016 Elsevier Inc. All rights reserved

Transparent exopolymer particles and Coomassie stainable particles show uncoupled distributions in the surface ocean

2018 Ocean Sciences Meeting, 11-16 February, in Portland, OregonTransparent exopolymer particles (TEP; composed mainly of polysaccharides) and Coomassie stainable particles (CSP; composed mainly of proteins) are two subclasses of organic particles that largely affect element cycling, sea-air interactions and food-web structure in the ocean. However, the little availability of in situ data hampers our understanding of the mechanisms through which these particles are cycled in the ocean. We quantified for the first time TEP and CSP concentrations in parallel in surface waters of contrasting oceanic regions (across the Atlantic, the Southern Ocean, and the coastal NW Mediterranean Sea), and explored the potential drivers of their distribution. TEP concentrations overall ranged from below detection limit to 80.9, and averaged 19.0 (±5.4), 31.4 (±14.4) and 34.1 (±20.1) µg XG eq L-1 in the Atlantic, Antarctic - Subantarctic, and NW Mediterranean waters, respectively. CSP concentrations overall ranged from below detection limit to 64.3, and averaged 5.9 (±5.9), 15.0 (±10.0) and 9.9 (±6.5) µg BSA eq L-1, respectively, in the same regions. Over a time series study in the NW Mediterranean, TEP concentrations presented their maxima in early summer, probably related to nutrient deficiency, whilst CSP showed their highest concentrations in early winter, associated with higher chlorophyll levels. The horizontal distributions of both particle types were uncoupled across the Atlantic Ocean, but correlated significantly in the Antarctic – Subantarctic (r=0.46, n=42, p-value=0.0027), suggesting that they have different drivers in oligotrophic areas but both are associated with phytoplankton in productive areas. Token samples were examined for vertical profiles and size distributions. The comparison of TEP and CSP stocks with a broad suite of environmental and biological variables will allow better understanding of particulate organic matter cycling in the upper ocean and its consequences for the biological carbon pumpPeer Reviewe

Notch receptor expression in Trypanosoma cruzi‐infected human umbilical vein endothelial cells treated with benznidazole or simvastatin revealed by microarray analysis

Chagas disease is a vector-borne disease caused by the protozoan parasite Trypanosoma cruzi. Current therapy involves benznidazole. Benznidazole and other drugs can modify gene expression patterns, improving the response to the inflammatory influx induced by T. cruzi and decreasing the endothelial activation or immune cell recruitment, among other effects. Here, we performed a microarray analysis of human umbilical vein endothelial cells (HUVECs) treated with benznidazole and the anti-inflammatory drugs acetylsalicylic acid or simvastatin and infected with T. cruzi. Parasitic infection produces differential expression of a set of genes in HUVECs treated with benznidazole alone or a combination with simvastatin or acetylsalicylic acid. The differentially expressed genes were involved in inflammation, adhesion, cardiac function, and remodeling. Notch1 and high mobility group B1 were genes of interest in this analysis due to their importance in placental development, cardiac development, and inflammation. Quantitative polymerase chain reaction confirmation of these two genes indicated that both are upregulated in the presence of benznidazole.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECY

Simvastatin and Benznidazole-Mediated Prevention of <i>Trypanosoma cruzi</i>-Induced Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin

<div><p><i>Trypanosoma cruzi</i> is the causal agent of Chagas Disease that is endemic in Latin American, afflicting more than ten million people approximately. This disease has two phases, acute and chronic. The acute phase is often asymptomatic, but with time it progresses to the chronic phase, affecting the heart and gastrointestinal tract and can be lethal. Chronic Chagas cardiomyopathy involves an inflammatory vasculopathy. Endothelial activation during Chagas disease entails the expression of cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) through a mechanism involving NF-κB activation. Currently, specific trypanocidal therapy remains on benznidazole, although new triazole derivatives are promising. A novel strategy is proposed that aims at some pathophysiological processes to facilitate current antiparasitic therapy, decreasing treatment length or doses and slowing disease progress. Simvastatin has anti-inflammatory actions, including improvement of endothelial function, by inducing a novel pro-resolving lipid, the 5-lypoxygenase derivative 15-epi-lipoxin A4 (15-epi-LXA4), which belongs to aspirin-triggered lipoxins. Herein, we propose modifying endothelial activation with simvastatin or benznidazole and evaluate the pathways involved, including induction of 15-epi-LXA4. The effect of 5 μM simvastatin or 20 μM benznidazole upon endothelial activation was assessed in EA.hy926 or HUVEC cells, by E-selectin, ICAM-1 and VCAM-1 expression. 15-epi-LXA4 production and the relationship of both drugs with the NFκB pathway, as measured by IKK-IKB phosphorylation and nuclear migration of p65 protein was also assayed. Both drugs were administered to cell cultures 16 hours before the infection with <i>T</i>. <i>cruzi</i> parasites. Indeed, 5 μM simvastatin as well as 20 μM benznidazole prevented the increase in E-selectin, ICAM-1 and VCAM-1 expression in <i>T</i>. <i>cruzi</i>-infected endothelial cells by decreasing the NF-κB pathway. In conclusion, Simvastatin and benznidazole prevent endothelial activation induced by <i>T</i>. <i>cruzi</i> infection, and the effect of simvastatin is mediated by the inhibition of the NFκB pathway by inducing 15-epi-LXA4 production.</p></div

Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target

Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose-matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC50 of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in infected BALB/c mice, pentamidine failed to get synergy with benznidazole, measured on mice survival, parasitemia and amastigote nest quantification. To further explain the in vitro antagonism, we explored whether pentamidine affects intracellular trypanothione levels, however, pentamidine produced no change in trypanothione concentrations. Finally, the T. cruzi polyamine permease (TcPAT12) was overexpressed in epimastigotes, showing that pentamidine has the same trypanocidal effect, independently of transporter expression levels. These results suggest that, in spite of the high potency in the putrescine transport blockade, TcPAT12 permease is not the main target of pentamidine, and could explain the lack of synergism between pentamidine and benznidazole.Fil: Seguel, Verónica. Universidad de Chile; ChileFil: Castro, Lorena. Universidad de Chile; ChileFil: Reigada, Chantal. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cortes, Leonel. Universidad de Chile; ChileFil: Díaz, María V.. Universidad de Chile; ChileFil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lapier, Michel. Universidad de Chile; ChileFil: Campos Estrada, Carolina. Universidad de Chile; ChileFil: Morello, Antonio. Universidad de Chile; ChileFil: Kemmerling, Ulrike. Universidad de Chile; ChileFil: Maya, Juan D.. Universidad de Chile; ChileFil: López Muñoz, Rodrigo. Universidad de Chile; Chil