Bovine colostrum supplementation improves bone metabolism in an osteoporosis-induced animal model

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.EC -European Commission(778277

Glia-Pinealocyte Network: The Paracrine Modulation of Melatonin Synthesis by Tumor Necrosis Factor (TNF)

The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status

Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Young people's political engagement in the hip-hop movement

What leads young people to engage in political activism, creating or participating in interest groups? This question is discussed in the light of results obtained from a research on a group of rappers involved with the hip-hop movement in the city of Campinas, São Paulo. Their dispositions toward activism are analyzed as a result of the objective and subjective conditions under which they were socialized, apprehended through a study of their family's social trajectory. In turn, their concrete engagement in political activities is seen as the never-permanent result of meetings and interactions developed inside networks of different kinds, including the affective ones, located in a social space that is made concrete through institutions and collective ways of acting and thinking that guide everyday micro-decisions, including those relative to political action.O que leva alguns jovens a se envolver com a militância política, criando ou participando de grupos de interesse? Essa questão é discutida a partir dos resultados de uma pesquisa sobre um grupo de rappers envolvido com o movimento hiphop na cidade de Campinas, estado de São Paulo. Suas disposições para a militância são analisadas como resultado das condições objetivas e subjetivas em que se deu sua socialização, apreendidas por meio do estudo da trajetória social de suas famílias. Por sua vez, a entrada concreta em militância é analisada como resultado, nunca definitivo, dos encontros e das interações desenvolvidas no interior de redes de relações de vários tipos, inclusive afetivas, que se localizam num espaço social concretizado em instituições, modos de agir e de pensar que orientam microdecisões cotidianas, incluindo aquelas associadas à ação política.¿Qué es lo que lleva a algunos jóvenes a envolverse con la militancia política, creando o participando de grupos de interés? Esta cuestión es discutida a partir de los resultados de un estudio sobre un grupo de rappers involucrado con el movimiento hip-hop en la ciudad de Campinas, estado de São Paulo. Sus disposiciones para la militancia son analizadas como resultado de las condiciones objetivas y subjetivas en que se dio su socialización, aprendidas a través del estudio de la trayectoria social de sus familias. Sin embargo, la entrada concreta en la militancia es analizada como resultado, nunca definitivo, de los encuentros y de las interacciones desarrolladas en el interior de redes de relaciones de varios tipos, inclusive afectivas, que se localizan en un espacio social concretizado en instituciones, modos de actuar y de pensar que orientan microdecisiones cotidianas, incluyendo aquellas asociadas a la acción política.13014

That's politics, man! militant socialization and the instutitionalization of social movements

How are militant associations created? Which elements and/or processes allow individuals to act as a group and create an organization aimed at interfering in the political sphere? We look into this question by studying a group of young black rappers who created their association in the late 1990's in Campinas, SP. Through long, repeated interviews and the observation of some of their encounters and practices, we show that the association was made possible by a learning process experienced by the rappers through their contact with older and experienced politicians. In the process, they learned how to organize a political movement in order to influence government policies. They also learned a number of activist techniques that helped them to be respected and to find support in other segments of party and syndicate activism. Through the association, the rappers made the Campinas hip hop movement concrete and visible and, in 2001, they obtained support from the Partido dos Trabalhadores city administration, for the creation of a House of Hip Hop, a center where they were employed to develop artistic and political activities.Como se cria uma associação militante? Que elementos e/ou processos são necessários para que indivíduos ajam como um grupo para criar uma organização destinada a atuar no espaço político? Esta questão foi discutida numa pesquisa que focalizou um grupo de jovens rappers negros que fundou uma associação no final dos anos 1990 em Campinas, SP. Por meio de longas, repetidas entrevistas e observações de alguns dos seus encontros e práticas, mostramos que a associação foi o resultado de um processo de aprendizagem por que passaram os jovens, ao longo de um contato estreito com políticos profissionais mais velhos e mais experientes. Nesse processo eles aprenderam como um movimento de protesto deveria se articular para influenciar o governo. Aprenderam também certas técnicas de mobilização que lhes permitiram ser respeitados e construir apoios em outros segmentos de ativismo partidário e sindical. As ações da associação deram concretude e visibilidade à idéia de que havia um movimento hip hop na cidade. Em 2001, ao final de uma longa negociação, seus membros obtiveram o apoio da prefeitura municipal da cidade, assumida pelo PT, para a criação da Casa do Hip Hop de Campinas, onde eles foram empregados para desenvolver atividades artísticas e políticas.597