Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH

Valorization, comparison and characterization of coconuts waste and cactus in a biorefinery context using NaClO2-C2H4O2 and sequential NaClO2-C2H4O2/autohydrolysis pretreatment

The search for new sources of lignocellulosic raw materials for the generation of energy and new compounds encourages the search for locations not well known and with a high potential for biomass availability as is the case of the Northeast Region of Brazil. Thus, the cactus (CAC), green coconut shell (GCS), mature coconut fibre and mature coconut shell were pretreated by NaClO2C2H4O2 and sequential NaClO2C2H4O2/autohydrolysis aiming at the obtention of high added-value compounds in the liquid fraction and solid phase. The yield of the solid phase was between 61.42 and 90.97% and the reduction up to 91.63% of lignin in the materials pretreated by NaClO2C2H4O2. After NaClO2C2H4O2/autohydrolysis pretreatment the obtained solids yield was between 43.57 and 52.08%, with a solubilization of the hemicellulose content up to 81.42%. For both pretreatments the cellulosic content remained almost unchanged. The pretreated solids were characterized by SEM, X-ray and crystallinity indexes showing significant modifications when submitted to pretreatments. These results were further confirmed by the enzymatic conversion yields of 81.6890.03 and 86.9790.36% of the LCMs pretreated by NaClO2C2H4O2 and pretreated by NaClO2C2H4O2/autohydrolysis, respectively. The resulting liquors had a total phenolic compounds content between 0.20 and 3.05 g/L, lignin recovered up to 7.40 g/L (absence of sulphur) and xylooligosaccharides between 16.13 and 20.37 g/L. Thus, these pretreatments showed an efficient fractionation of LCMs, especially in the GCS, being an important requirement for the generation of products and byproducts in the context of the biorefinery.The authors gratefully acknowledge the Brazilian research funding agencies CNPq and CAPES for financial support. Financial support from the Energy Sustainability Fund 2014-05 (CONACYT-SENER), Mexican Centre for Innovation in Bioenergy (CemieBio), Cluster of Bioalcohols (Ref. 249564) is gratefully acknowledged. We also gratefully acknowledge support for this research by the Mexican Science and Technology Council (CONACYT, Mexico) for the infrastructure project - INFR201601 (Ref. 269461) and CB-2015-01 (Ref. 254808).info:eu-repo/semantics/publishedVersio

Vulnerability of Brazilian municipalities to hantavirus infections based on multi‑criteria decision analysis

Background: Hantavirus infection is an emerging zoonosis transmitted by wild rodents. In Brazil, high case-fatality rates among humans infected with hantavirus are of serious concern to public health authorities. Appropriate preventive measures partly depend on reliable knowledge about the geographical distribution of this disease. Methods: Incidence of hantavirus infections in Brazil (1993–2013) was analyzed. Epidemiological, socioeconomic, and demographic indicators were also used to classify cities’ vulnerability to disease by means of multi-criteria decision analysis (MCDA). Results: From 1993 to 2013, 1752 cases of hantavirus were registered in 16 Brazilian states. The highest incidence of hantavirus was observed in the states of Mato Grosso (0.57/100,000) and Santa Catarina (0.13/100,000). Based on MCDA analysis, municipalities in the southern, southeastern, and midwestern regions of Brazil can be classified as highly vulnerable. Most municipalities in northern and northeastern Brazil were classified as having low vulnerability to hantavirus cardiopulmonary syndrome. Conclusions: Although most human infections by hantavirus registered in Brazil occurred in the southern region of the country, a greater vulnerability to hantavirus was found in the Brazilian Midwest. This result reflects the need to strengthen surveillance where the disease has thus far gone unreported

Errores de medicación en pediatría

Concerns regarding patient safety affect healthcare, and medication errors are the most frequent category of medical errors and linked with severe consequences. This study discusses epidemiologic characteristics of medication errors in pediatric patients and points out prevention strategies. Approximately 8% of the studies on the subject of medication errors identified in different national and international databases are distinctively related to the pediatric population. Children are vulnerable to medication errors due to intrinsic factors, such as proper anatomic and physiological characteristics; and due to extrinsic factors, with emphasis on the lack of public health politics and changes in the pharmaceutical industry to attend children's needs. The available evidences indicate, as imperative, the implementation of strategies to prevent medication errors, contributing to promote patient safety.La seguridad del paciente es un problema de salud pública y los errores con medicamentos son los más frecuentes y más graves. Este artículo describe características epidemiológicas de errores de medicación en áreas de atención pediátrica y algunas estrategias de prevención. Aproximadamente 8% de las investigaciones sobre errores de medicación identificadas en las bases de datos nacionales e internacionales se refieren específicamente a niños. Los niños tienen mayor vulnerabilidad a la ocurrencia de errores debidos a factores intrínsecos, con destaque para características anatómicas y fisiológicas, e extrínsecos, en particular con respecto a falta de políticas sanitarias y de la industria farmacéutica orientada a la atención de tales características. Evidencias muestran la necesidad de aplicar estrategias para prevenir errores de medicación, promoviendo la seguridad del paciente.A segurança do paciente constitui problema de saúde pública, e erros com medicamentos são os mais freqüentes e graves. O artigo apresenta características epidemiológicas dos erros de medicação em diferentes áreas de atendimento pediátrico, e aponta estratégias de prevenção. Aproximadamente 8% das pesquisas sobre erros de medicação identificadas em bases de dados nacionais e internacionais referem-se à população pediátrica. Crianças apresentam maior vulnerabilidade à ocorrência de erros devido a fatores intrínsecos, destacando-se características anatômicas e fisiológicas; e extrínsecos, relativos à falta de políticas de saúde e da indústria farmacêutica voltadas ao atendimento de tais especificidades. As evidências apontam para a necessidade de implementação de estratégias de prevenção de erros de medicação, contribuindo para promover a segurança do paciente.Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemSciEL

Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. METHODS: Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. RESULTS: All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. CONCLUSION: Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.We thank the Portuguese Science and Technology Foundation (FCT) for VMG fellowship (ref. SFRH/BI/33503/2008). The authors thank Mr. Antonio Marques from Frutercoop - Azores, who kindly collected and provided the propolis sample for the study