Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10–20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma - ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP). Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 also reduced GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL

Quantifying the third sector in Portugal : an overview and evolution from 1997 to 2007

I am grateful to the Portuguese Ministry of Labor and Social Solidarity, Statistics Department, for access to the data used in this study (Quadros de Pessoal). I would also like to express my gratitude to Miguel Reis Portela and Nelson Areal for their assistance in dealing with the database and STATA. I am also indebted to two anonymous reviewers for their useful comments on an earlier version of this paper.This paper presents a global overview of the third sector in Portugal drawing on data from a linked employer-employee database – “Quadros de Pessoal”, which is based on a compulsory annual inquiry to organizations, making it a better source of information than those based on sample surveys and estimates. This study advances on previous overviews by providing more updated numbers for organization size, age, gross revenue and employment levels, as well as their distribution across the ICNPO third sector activity classification. The evolution of these variables from the period 1997-2007 is also analyzed. The Portuguese third sector has been fast growing, with revenues amounting to 5.64% of Portugal’s GDP and employment representing 4% of the country’s employment in 2007. It is mainly composed of very small organizations, with diminutive revenues. Perhaps its most striking features are the uneven distribution of employment and revenue and the strong concentration on Social services

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

Current distribution of Achatina fulica, in the State of São Paulo including records of Aelurostrongylus abstrusus (Nematoda) larvae infestation

The currently known distribution range of Achatina fulica Bowdich, 1822, in the state of São Paulo, Brazil, is presented. The record of A. fulica naturally infested with Aelurostrongylus abstrusus larvae (Railliet, 1898) (Nematoda: Metastrongylidae) can be found in the city of Guaratinguetá. It was found A. fulica with Metastrongylidae larvae without known medical and veterinary importance in the cities of Carapicuíba, Embu-Guaçu, Itapevi, São Caetano do Sul, São Paulo and Taboão da Serra.É apresentada a distribuição de Achatina fulica Bowdich, 1822 no Estado de São Paulo, Brasil. É fornecido o registro de A. fulica naturalmente infestada por larvas de Aelurostrongylus abstrusus (Railliet, 1898) (Nematoda: Metastrongylidae) no município de Guaratinguetá. Foi encontrada A. fulica portando larvas de Metastrongylidae sem importância médica e veterinária conhecida nos municípios de Carapicuíba, Embu Guaçu, Itapevi, São Caetano do Sul, São Paulo e Taboão da Serra

Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

<p>Abstract</p> <p>Background</p> <p>Infections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 μg/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 μg/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment.</p> <p>Results</p> <p>All three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 μg/mL) of SFG, IS and ID.</p> <p>Conclusion</p> <p>These data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings.</p