Novedades terapéuticas en el tratamiento del asma

International audienc

The water balance in Mendoza : measurement proposals

La Ley N°8051/2009 de Ordenamiento Territorial y Usos del Suelo de Mendoza subraya la importancia de considerar la disponibilidad de agua para garantizar un uso equilibrado del territorio. La Ley General de Aguas de 1884 y la Constitución Provincial de 1916 destacan la necesidad de verificar la existencia de excedentes hídricos previa a la entrega de nuevas concesiones. Considerando al balance hídrico como un elemento para el manejo de la sustentabilidad del recurso hídrico y del suelo, los objetivos del presente estudio son: describir los componentes del balance para las cuencas de Mendoza, proponer alternativas para su medición y esclarecer su incidencia en la planificación del territorio. El balance hídrico se mide a nivel de cuenca o subcuenca y se entiende como la diferencia entre la oferta y la demanda de agua, para verificar la existencia de excedentes. La oferta proviene de los aforos de los ríos y de evaluaciones de recarga subterránea y está afectada cuantitativamente por la contaminación. La demanda está integrada por los diferentes usos: doméstico, riego, industrial, municipal y ambiental. Se discuten y proponen alternativas de estimación para los términos de la demanda. Ante la falta de mediciones directas sobre los elementos que integran la demanda, se recomienda realizar mediciones indirectas utilizando coeficientes de uso de agua por unidad de consumo. Se sugiere modelizar el balance hídrico como variable importante para la construcción de escenarios alternativos y del modelo territorial deseado.Law 8051 of Land Use Planning and Soil Use in Mendoza, which was passed in 2009, recognizes the importance of considering water availability to ensure a balanced use of the land. The Water Law of 1884 and the Provincial Constitution of 1916 refer to the need to check the existence of water surpluses before granting new water use permits. Since water balance is a crucial element for managing water and soil sustainability, the objectives of this study are to describe the system’s components in the Mendoza basins, to propose measurement alternatives and to explore its impact on land use planning. The water balance is measured at the basin or sub-basin level and since it is considered as the difference between water supply and demand, it is possible to check the existence of water surpluses. The water supply comes from river gauging and from groundwater recharge. Water supply is affected by surface and groundwater pollution. Water demand comes from different uses: domestic, irrigation, industrial, municipal and environmental. Assessment alternatives are discussed and proposed. Given the lack of direct measurements of water demand, it is recommended to conduct indirect measurements using water use coefficients per unit of consumption. The study proposes to model the water balance as a relevant variable to construct alternative scenarios and to apply them to the intended land use model.Fil: Llop, Armando A.. Instituto Nacional del Agua. Centro de Economía, Legislación y Administración del AguaFil: Fasciolo, Graciela. Instituto Nacional del Agua. Centro de Economía, Legislación y Administración del AguaFil: Duek, Alicia E.. Instituto Nacional del Agua. Centro de Economía, Legislación y Administración del AguaFil: Comellas, Eduardo A.. Instituto Nacional del Agua. Centro de Economía, Legislación y Administración del AguaFil: Buccheri, Mauricio J.. Instituto Nacional del Agua. Centro de Economía, Legislación y Administración del Agu

Oral Treatment with Iododiflunisal Delays Hippocampal Amyloid-β Formation in a Transgenic Mouse Model of Alzheimer's Disease: A Longitudinal in vivo Molecular Imaging Study

Transthyretin (TTR) is a tetrameric, amyloid-β (Aβ)-binding protein, which reduces Aβ toxicity. The TTR/Aβ interaction can be enhanced by a series of small molecules that stabilize its tetrameric form. Hence, TTR stabilizers might act as disease-modifying drugs in Alzheimer's disease. Objective: We monitored the therapeutic efficacy of two TTR stabilizers, iododiflunisal (IDIF), which acts as small-molecule chaperone of the TTR/Aβ interaction, and tolcapone, which does not behave as a small-molecule chaperone, in an animal model of Alzheimer's disease using positron emission tomography (PET). Methods: Female mice (AβPPswe/PS1A246E/TTR+/-) were divided into 3 groups (n=7 per group): IDIF-treated, tolcapone-treated, and non-treated. The oral treatment (100mg/Kg/day) was started at 5 months of age. Treatment efficacy assessment was based on changes in longitudinal deposition of Aβ in the hippocampus (HIP) and the cortex (CTX) and determined using PET-[18F]florbetaben. Immunohistochemical analysis was performed at age=14 months. Results: Standard uptake values relative to the cerebellum (SUVr) of [18F]florbetaben in CTX and HIP of non-treated animals progressively increased from age=5 to 11 months and stabilized afterwards. In contrast, [18F]florbetaben uptake in HIP of IDIF-treated animals remained constant between ages=5 and 11 months and significantly increased at 14 months. In the tolcapone-treated group, SUVr progressively increased with time, but at lower rate than in the non-treated group. No significant treatment effect was observed in CTX. Results from immunohistochemistry matched the in vivo data at age=14 months. Conclusion: Our work provides encouraging preliminary results on the ability of small-molecule chaperones to ameliorate Aβ deposition in certain brain regions

Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis

Altres ajuts: This work was supported by the EU FP7-MINECO Infect-ERA Program, and Red Española de Esclerosis Múltiple (REEM) from the Instituto de Salud Carlos III, the European Regional Development Fund (Grant RD16/0015/0011), and the Spanish Ministry of Economy and Competitiveness.Human cytomegalovirus (HCMV) infection has been recently associated with a low risk of multiple sclerosis (MS), yet the basis behind this observation remains uncertain. In this study, we aimed to determine in MS patients whether HCMV induces modifications in the peripheral B cell compartment. HCMV serostatus was determined in 73 MS patients (55 relapsing-remitting MS (RRMS); 18 progressive MS (PMS)) and 30 healthy controls, assessing their B cell immunophenotype and cytokine production (GM-CSF, IL-6, IL-10, and TNFα) by flow cytometry. HCMV seropositivity in untreated MS patients (n = 45) was associated with reduced switched memory B cells, contrasting with an opposite effect in PMS. Expansions of transitional B cells were observed in HCMV(+) IFNβ-treated RRMS patients but not in HCMV(−) cases (p < 0.01), suggesting that HCMV may influence the distribution of B cell subsets modulating the effects of IFNβ. Considering the B cell functional profile, HCMV(−) PMS displayed an increased secretion of proinflammatory cytokines (IL-6, TNFα) as compared to HCMV(+) PMS and RRMS cases (p < 0.001). Our study reveals an influence of HCMV infection on the phenotype and function of B cells, promoting early differentiation stages in RRMS and reducing the proinflammatory cytokine profile in advanced MS forms, which might be related with the putative protective role of this virus in MS

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study

AbstractBackgroundATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models.AimsTo evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes.Materials and methodsNutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008–2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers.ResultsSeven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores.DiscussionGenetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated

GlycoForm and Glycologue: two software applications for the rapid construction and display of N-glycans from mammalian sources

<p>Abstract</p> <p>Background</p> <p>The display of <it>N</it>-glycan carbohydrate structures is an essential part of glycoinformatics. Several tools exist for building such structures graphically, by selecting from a palette of symbols or sugar names, or else by specifying a structure in one of the chemical naming schemes currently available.</p> <p>Findings</p> <p>In the present work we present two tools for displaying <it>N</it>-glycans found in the mammalian CHO (Chinese hamster ovary) cell line, both of which take as input a 9-digit identifier that uniquely defines each structure. The first of these, GlycoForm, is designed to display a single structure automatically from an identifier entered by the user. The display is updated in real time, using symbols for the sugar residues, or in text-only form. Structures can be added to a library, which is recorded in a preference file and loaded automatically at start. Individual structures can be saved in a variety of bitmap image formats. The second program, Glycologue, reads a file containing columnar data of nine-digit codes, which can be displayed on-screen and printed at high resolution.</p> <p>Conclusion</p> <p>A key advantage of both programs is the speed and facility with which carbohydrate structures can be drawn. It is anticipated that these programs will be useful to glycobiologists, systems biologists and biotechnologists interested in <it>N</it>-glycosylation systems in mammalian cells.</p