Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans

RATIONALE: Purpura fulminans in adults is a rare but devastating disease. Its pathophysiology is not well known. OBJECTIVES: To understand the pathophysiology of skin lesions in purpura fulminans, the interplay between circulating blood and vascular alterations was assessed. METHODS: Prospective multicenter study in four intensive care units. Patients with severe sepsis without skin lesions were recruited as control subjects. MEASUREMENTS AND MAIN RESULTS: Twenty patients with severe sepsis and purpura fulminans were recruited for blood sampling, and skin biopsy was performed in deceased patients. High severity of disease and mortality rates (80%) was observed. Skin biopsies in purpura fulminans lesions revealed thrombosis and extensive vascular damage: vascular congestion and dilation, endothelial necrosis, alteration of markers of endothelial integrity (CD31) and of the protein C pathway receptors (endothelial protein C receptor, thrombomodulin). Elevated plasminogen activating inhibitor-1 mRNA was also observed. Comparison with control patients showed that these lesions were specific to purpura fulminans. By contrast, no difference was observed for blood hemostasis parameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coagulation markers. Bacterial presence at the vascular wall was observed specifically in areas of vascular damage in eight of nine patients tested (including patients with Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, and Pseudomonas aeruginosa infection). CONCLUSIONS: Thrombi and extensive vascular damage with multifaceted prothrombotic local imbalance are characteristics of purpura fulminans. A "vascular wall infection" hypothesis, responsible for endothelial damage and subsequent skin lesions, can be put forward

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults

Background: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. Methods: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. Results: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68–75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006–0.0015) and 0.0015 (0.0007–0.0023) g/cm2, respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007–0.0016) and 0.0017 (0.0010–0.0024) g/cm2, respectively]. Plant protein intake was associated with a lower total body and spine BMD [−0.0010 (−0.0020 to −0.0001) and −0.0019 (−0.0034 to −0.0004) g/cm2, respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70–81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. Conclusions: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed

Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

Previous studies have documented that the insulin-producing β-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes β-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with β-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of β-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the β-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human β-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing β-cells, and contributes to control β-cell function by modulating gene expressio

Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with beta-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of beta-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the beta-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human beta-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing beta-cells, and contributes to control beta-cell function by modulating gene expression.The Swiss National Science Foundation (310000-122430 to P.Me), the Juvenile Diabetes Research Foundation (1-2005-1084 to V.C., 1-2007-158 to P.Me), the National Institute of Health (DK55183 to V.C.), the European Union (FP6-Integrated Project EuroDia LSHM-CT-2006-518153 to P.Ma; FP-7 BETAIMAGE 222980 to P.Me), Novo Nordisk (to P.Me) and The Larry L. Hillblom Foundation (to V.C.). Image analysis was performed at The National Center for Microscopy and Imaging Research (NIH grant RR4050 to M. Ellisman). Fresh human islets were provided by the Cell Isolation and Transplantation Cente

Transferencia de tecnología para cocción energéticamente eficiente en ciudades de la Patagonia argentina

El presente trabajo describe el proceso de realización de taller de cajas térmicas y hornos solares en dos localidades de la Patagonia Argentina, Sierra Grande (Río Negro) y Puerto Madryn (Chubut). A través de la convocatoria efectuada por la Fundación Patagona Natural, se realizaron dos talleres de autoconstrucción de hornos solares de tacho y uno de cajas térmicas, esta actividad se llevó a cabo como complemento de un trabajo previo con las comunidades como lo es la fabricación de composteras. La radiación solar global diaria en verano en la zona en estudio es de 7 kWh/m2 día; con lo cual se podría utilizar el horno solar en esa época. Los talleres se desarrollaron a través de la intervención participativa entre los capacitadores y los participantes, futuros usuarios de los equipos. El seguimiento del los grupos se lleva a cabo por miembros de la Fundación Patagonia Natural y por el equipo capacitador a través de intervenciones de los propios usuarios en redes sociales. Se observan logros interesantes tanto en el uso de la tecnología como en la réplica posterior a la realización de los talleres, lo cual pone énfasis en las ventajas de la metodología empleada.Tema 10: Educación y capacitación en energías renovables y uso racional de la energía.Facultad de Arquitectura y Urbanism

Transferencia de tecnología para cocción energéticamente eficiente en ciudades de la Patagonia argentina

El presente trabajo describe el proceso de realización de taller de cajas térmicas y hornos solares en dos localidades de la Patagonia Argentina, Sierra Grande (Río Negro) y Puerto Madryn (Chubut). A través de la convocatoria efectuada por la Fundación Patagona Natural, se realizaron dos talleres de autoconstrucción de hornos solares de tacho y uno de cajas térmicas, esta actividad se llevó a cabo como complemento de un trabajo previo con las comunidades como lo es la fabricación de composteras. La radiación solar global diaria en verano en la zona en estudio es de 7 kWh/m2 día; con lo cual se podría utilizar el horno solar en esa época. Los talleres se desarrollaron a través de la intervención participativa entre los capacitadores y los participantes, futuros usuarios de los equipos. El seguimiento del los grupos se lleva a cabo por miembros de la Fundación Patagonia Natural y por el equipo capacitador a través de intervenciones de los propios usuarios en redes sociales. Se observan logros interesantes tanto en el uso de la tecnología como en la réplica posterior a la realización de los talleres, lo cual pone énfasis en las ventajas de la metodología empleada.Tema 10: Educación y capacitación en energías renovables y uso racional de la energía.Facultad de Arquitectura y Urbanism

Transferencia de tecnología para cocción energéticamente eficiente en ciudades de la Patagonia argentina

El presente trabajo describe el proceso de realización de taller de cajas térmicas y hornos solares en dos localidades de la Patagonia Argentina, Sierra Grande (Río Negro) y Puerto Madryn (Chubut). A través de la convocatoria efectuada por la Fundación Patagona Natural, se realizaron dos talleres de autoconstrucción de hornos solares de tacho y uno de cajas térmicas, esta actividad se llevó a cabo como complemento de un trabajo previo con las comunidades como lo es la fabricación de composteras. La radiación solar global diaria en verano en la zona en estudio es de 7 kWh/m2 día; con lo cual se podría utilizar el horno solar en esa época. Los talleres se desarrollaron a través de la intervención participativa entre los capacitadores y los participantes, futuros usuarios de los equipos. El seguimiento del los grupos se lleva a cabo por miembros de la Fundación Patagonia Natural y por el equipo capacitador a través de intervenciones de los propios usuarios en redes sociales. Se observan logros interesantes tanto en el uso de la tecnología como en la réplica posterior a la realización de los talleres, lo cual pone énfasis en las ventajas de la metodología empleada.Tema 10: Educación y capacitación en energías renovables y uso racional de la energía.Facultad de Arquitectura y Urbanism

Comparison of root absorption, translocation and tolerance of arsenic in the hyperaccumulator Pteris vittata and the nonhyperaccumulator Pteris tremula

Several fern species can hyperaccumulate arsenic, although the mechanisms are not fully understood. Here we investigate the roles of root absorption, translocation and tolerance in As hyperaccumulation by comparing the hyperaccumulator Pteris vittata and the nonhyperaccumulator Pteris tremula. The two species were grown in a pot experiment with 0-500 mg As kg(-1) added as arsenate, and in a short-term (8 h) uptake experiment with 5 pm arsenate under phosphorus-sufficient conditions. In the pot experiment, P. vittata accumulated up to 2500 mg As kg(-1) frond d. wt and suffered no phytotoxicity. P. tremula accumulated < 100 mg As kg(-1) frond d. wt and suffered severe phytotoxicity with additions of ! 25 mg As kg-1. In the short-term uptake experiment, P. vittata had a 2.2-fold higher rate of arsenate uptake than P. tremula, and distributed more As taken up to the fronds (76%) than did P. tremula (9%). Our results show that enhanced root uptake, efficient root-to-shoot translocation, and a much elevated tolerance through internal detoxification all contribute to As hyperaccumulation in P. vittata

Cyclic stretch increases splicing noise rate in cultured human fibroblasts

BACKGROUND: Mechanical forces are known to alter the expression of genes, but it has so far not been reported whether they may influence the fidelity of nucleus-based processes. One experimental approach permitting to address this question is the application of cyclic stretch to cultured human fibroblasts. As a marker for the precision of nucleus-based processes, the number of errors that occur during co-transcriptional splicing can then be measured. This so-called splicing noise is found at low frequency in pre-mRNA splicing. FINDINGS: The amount of splicing noise was measured by RT-qPCR of seven exon skips from the test genes AATF, MAP3K11, NF1, PCGF2, POLR2A and RABAC1. In cells treated by altered uniaxial cyclic stretching for 18 h, a uniform and significant increase of splicing noise was found for all detectable exon skips. CONCLUSION: Our data demonstrate that application of cyclic stretch to cultured fibroblasts correlates with a reduced transcriptional fidelity caused by increasing splicing noise