Body composition and body fat distribution are related to cardiac autonomic control in non-alcoholic fatty liver disease patients

BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control marker, was shown to be related to body composition (BC), yet this was not tested in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to determine if, and to what extent, markers of BC and body fat (BF) distribution are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men, 51±13 years, and 9 women, 47±13 years). BF depots ratios were calculated to assess BF distribution. Subjects’ HRR was recorded 1 (HRR1) and 2 min (HRR2) immediately after a maximum graded exercise test. RESULTS: BC and BF distribution were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular BF ratio showed a negative relation with HRR1 (r 1⁄4 0.613, r 1⁄4 0.597 and r 1⁄4 0.547, respectively, Po0.01) and HRR2 (r 1⁄4 0.484, r 1⁄4 0.446, Po0.05, and r 1⁄4 0.590, Po0.01, respectively). Age seems to be related to both HRR1 and HRR2 except when controlled for BF distribution. The preferred model in multiple regression should include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2 1⁄4 0.549; Po0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2 1⁄4 0.430; Po0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of HRR and therefore may be best related to cardiovascular increased risk, and possibly act as a mediator in age-related cardiac autonomic control variation.info:eu-repo/semantics/publishedVersio

The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice

Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5×106 trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased: initially (at 24 h) as diffuse infiltrates affecting the whole parenchyma, and at 48 h, in the form of large focal infiltrates in both the parenchyma and perivascular spaces. Phenotypic characterization of liver-infiltrating cells 24 h after challenge revealed an increase in Mac1+, CD8+ and CD4+ cells, followed by natural killer (NK) cells. As evidence that liver-infiltrating CD4+ and CD8+ cells were activated, increased frequencies of CD69+CD8+, CD69+CD4+ and CD25+CD122+CD4+ cells were observed at 24 and 48 h after challenge, and of CD25−CD122+CD4+ cells at 48 h. The major role of CD4+ cells in liver protection was suggested by data showing a very high frequency of interferon (IFN)-γ-producing CD4+ cells 24 h after challenge. In contrast, liver CD8+ cells produced little IFN-γ, even though they showed an enhanced potential for secreting this cytokine, as revealed by in vitro T cell receptor (TCR) stimulation. Confirming the effectiveness of the liver immune response in blood parasite control during the chronic phase of infection, no live parasites were detected in this organ 7 days after challenge

Volume, patterns, and types of sedentary behavior and cardio-metabolic health in children and adolescents: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Cardio-metabolic risk factors are becoming more prevalent in children and adolescents. A lack of moderate-to-vigorous intensity physical activity (MVPA) is an established determinant of cardio-metabolic risk factors in children and adolescents. Less is known about the relationship between sedentary behavior and cardio-metabolic health. Therefore, the objective was to examine the independent associations between volume, patterns, and types of sedentary behavior with cardio-metabolic risk factors among children and adolescents.</p> <p>Methods</p> <p>The results are based on 2527 children and adolescents (6-19 years old) from the 2003/04 and 2005/06 National Health and Nutrition Examination Surveys (NHANES). A cardio-metabolic risk score (CRS) was calculated based on age- and sex-adjusted waist circumference, systolic blood pressure, non-high-density lipoprotein cholesterol, and C-reactive protein values. Volume and patterns of sedentary behavior and moderate-to-vigorous physical activity (MVPA) were measured objectively using accelerometers. Types of sedentary behavior were measured by questionnaire. A series of logistic regression models were used to examine associations.</p> <p>Results</p> <p>Volume and patterns of sedentary behavior were not predictors of high CRS after adjusting for MVPA and other confounders (P > 0.1). For types of sedentary behavior, high TV use, but not high computer use, was a predictor of high CRS after adjustment for MVPA and other confounders. Children and adolescents who watched ≥4 hours per day of TV were 2.53 (95% confidence interval: 1.45-4.42) times more likely to have high CRS than those who watched <1 hour per day. MVPA predicted high CRS after adjusting for all sedentary behavior measures and other confounders. After adjustment for waist circumference, MVPA also predicted high non-obesity CRS; however, the same relationship was not seen with TV use.</p> <p>Conclusion</p> <p>No association was observed between overall volume and patterns of sedentary behavior with cardio-metabolic risk factors in this large sample of children and adolescents. Conversely, high TV use and low MVPA were independently associated with cardio-metabolic risk factors. However, the association between high TV use and clustered cardio-metabolic risk factors appears to be mediated or confounded by obesity. Thus, TV and MVPA appear to be two separate behaviors that need to be targeted with different interventions and policies.</p

Importance of TLR2 on Hepatic Immune and Non-Immune Cells to Attenuate the Strong Inflammatory Liver Response During Trypanosoma cruzi Acute Infection

Trypanosoma cruzi, an obligate intracellular protozoan, is the etiological agent of Chagas Disease that represents an important public health burden in Latin America. The infection with this parasite can lead to severe complications in cardiac, liver and gastrointestinal tissue depending on the strain of parasite and host genetics. Recently, we reported a fatal liver injury in T. cruzi infected B6 mice. However, the local immune response against this parasite is poorly understood. This work highlights some of the molecular and cellular mechanisms involved in liver pathology during the acute phase of infection. Using two mouse strains with different genetic backgrounds and responses to infection, B6 and BALB/c, we found that infected B6 mice develop a strong pro-inflammatory environment associated with high TLR9 expression. Conversely, infected BALB/c mice showed a more balanced inflammatory response in liver. Moreover, higher TLR2 and TLR4 expression were found only in hepatocytes from BALB/c. These data emphasize the importance of an adequate integration of signalling between immune and non-immune cells to define the outcome of infection. In addition, the pre-treatment with TLR2-agonist reverts the strong pro-inflammatory environment in T. cruzi infected B6 mice. These results could be useful in the understanding and design of novel immune strategies in controlling liver pathologies

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy

A Pilot Study on Developing Mucosal Vaccine against Alveolar Echinococcosis (AE) Using Recombinant Tetraspanin 3: Vaccine Efficacy and Immunology

Humans and rodents become infected with E. multilocularis by oral ingesting of the eggs, which then develop into cysts in the liver and progress an endless proliferation. Untreated AE has a fatality rate of >90% in humans. Tetraspanins have been identified in Schistosoma and showed potential as the prospective vaccine candidates. In our recent study, we first identified seven tetraspanins in E. multilocularis and evaluated their protective efficacies as vaccines against AE when subcutaneously administered to BALB/c mice. Mucosal immunization of protective proteins is able to induce strong local and systemic immune responses, which might play a crucial role in protecting humans against E. multilocularis infection via the intestine, blood and liver. We focused on Em-TSP3, which achieved significant vaccine efficacy via both s.c. and i.n. routes. The adjuvanticity of nontoxic CpG OND as i.n. vaccine adjuvant was evaluated. The widespread expression of Em-TSP3 in all the developmental stages of E. multilocularis, and the strong local and systemic immune responses evoked by i.n. administration of rEm-TSP3 with CpG OND adjuvant suggest that this study might open the way for developing efficient, nontoxic human mucosal vaccines against AE

Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats

Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-a-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.This work was supported by the Marie Curie Fellowship FP7-PEOPLE-2010-IEF 273936, BIAL Foundation Grants 138/2008 and 61/2010, FEDER funds through Operational program for competitiveness factors-COMPETE -, ON2 Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN/FEDER, and by national funds through FCT-Foundation for Science and Technology-project (PTDC/SAU-NSC/118194/2010) and fellowships (SFRH/BPD/66151/2009 and SFRH/BD/89714/2012)

Sedentary behavior among Spanish children and adolescents: findings from the ANIBES study

Background: An increase of sedentary behaviors far from the Mediterranean lifestyle is happening in spite of the impact on health. The aims of this study were to describe sedentary behaviors in children and adolescents. Methods: A representative sample of 424 Spanish children and adolescents (38% females) involved in the ANIBES study was analyzed regarding their sedentary behaviors, together with the availability of televisions, computers, and consoles by means of the HELENA sedentary behavior questionnaire. Results: For the total sample of children, 49.3% during weekdays and 84% during weekends did not meet the recommendation of less than 2 hours of screen viewing per day. The use of TV was higher during weekdays (p < 0.05) and there were significant differences between adolescents and children (16.9 vs. 25.1%, p < 0.05). The use of computer, console games and of internet for non-study reasons was higher during weekends (p < 0.001). Adolescents played more computer games and used more internet for non-study reasons than children during both weekdays and weekends (p < 0.05 and p < 0.001, respectively). The use of internet for academic reasons was lower in children (p < 0.001) than adolescents during weekends; however, no significant differences were found between sexes. In addition, more than 30% of the children and adolescents had at least one electronic device in their bedrooms. Conclusions: Spanish children and adolescents are not meeting the recommendations regarding the maximum of screen viewing (<2 h/day), especially during the weekend, for all of sedentary behaviors. Urgent strategies and intervention studies are needed to reduce sedentary behavior in young people.The ANIBES study was financially supported by a grant from Coca-Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data; in the writing of the manuscript, and in the decision to publish the results

Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile

In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE2 we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Iab and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens