Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes.

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement.

Immunosafe(r)-by-design nanoparticles: Molecular targets and cell signaling pathways in a next-generation model proxy for humans.

Nanotechnology research covers a wide field of studies pointing to design and shape complex matter in a scale between 1 and 100nm, with unique size-depending properties and applications. The value and potential of engineered nanoparticles in human diagnostics and therapies essentially relay on their safety and biocompatibility. Entering a cell, in fact, these particles take complex interactions with the surrounding biological environment, dramatically changing their own identity. The formation of a custom-made protein corona is the first signal of their interplay with the cell defensive mechanisms, and a major issue in their application in medicine. Preliminary in-depth studies in model organisms have been developed to assess immunological safety and competence in facing the host immune system and its defensive response. New affordable animal models are emerging in pilot nano-response and safety studies. Sea urchins, benthic marine Echinoderms, have a wide and very efficient immune system working with innate defense mechanisms and are widely used in immune studies. Nano-safety studies have been showing that the sea urchin Paracentrotus lividus displays an excellent sensing system and high defensive capability, joined to the availability of easily accessible immune cells. As in mammals, nanoparticle recognition and interaction activate specific signaling pathways, metabolic rewiring and homeostasis maintenance. In this chapter, we point to the value of planning new research and developing nano-immune studies using an easy nonmammalian next-generation model, able to unravel new specific response mechanisms to nanoparticles.

Estudio del índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida / Study of the level/dose index of phenytoin in volunteer epileptic patients from Mérida

INTRODUCCIÓN La fenitoína es usada con mucha frecuencia en nuestro medio, por lo que se requiere hacer estudios de monitorización terapéutica, que contribuya a minimizar los efectos adversos y optimizar la terapia farmacológica. En ese contexto, nuestro objetivo ha sido determinar el índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida. MÉTODOS Se realizó un estudio descriptivo, observacional y por reclutamiento consecutivo concurrente, conformado por 30 pacientes voluntarios con diagnóstico de epilepsia. Las muestras de suero se obtuvieron en niveles mínimos de pacientes que estaban en tratamiento con fenitoína durante 1 mes. Los niveles del fármaco se cuantificaron por el método de Inmunoensayo de enzima donante clonada en el equipo Indiko Thermo Scientific. RESULTADOS El índice nivel/dosis fue de 1,4 y 1,6, la concentración plasmática de 4,8mg/l y 8,0mg/l, la capacidad metabólica de 388,4 y 462,9mg/día, respectivamente en mujeres y hombres. Mientras que el nivel de la concentración plasmática en el estado estacionario fue de 6,5mg/l y 5,5mg/l, la dosis de carga máxima de 237,3mg y de 395,6mg, respectivamente en mujeres y hombres con epilepsia de la ciudad de Mérida. CONCLUSIONES Nuestros resultados sugieren que se debe individualizar la dosis en base al índice nivel/dosis de cada paciente, ya que no se puede extrapolar para todos los pacientes con epilepsia, debido a diversos factores como al fenotipo metabólico y al uso de fármacos inductores e inhibidores enzimáticos.

INTRODUCTION Phenytoin is used very frequently in our environment, so it is necessary to do studies of therapeutic monitoring, which helps to minimize adverse drug reaction and optimize pharmacological therapy. In this context, our objective was to determine the level/dose index of phenytoin in volunteer epileptic patients from Mérida. METHODS A descriptive, observational and consecutive concurrent recruitment study was carried out, consisting of 30 volunteer patients with a diagnosis of epilepsy. The serum samples were obtained in minimum levels from patients who were in treatment with phenytoin for 1 month. The levels of the drug were quantified by the method of donor enzyme immunoassay cloned in the Indiko Thermo Scientific equipment. RESULTS The level/dose index was 1,4 and 1,6, the plasma concentration of 4,8mg/l and 8,0mg/l, the metabolic capacity of 388,4 and 462,9mg/day, respectively in women and men. While the level of plasma concentration at steady state was 6,5mg/l and 5,5mg/l, the maximum loading dose of 237,3mg and 395,6mg, respectively in women and men with epilepsy of the city of Mérida. CONCLUSIONS Our results suggest that the dose should be individualized based on the level/dose index of each patient, since it can not be extrapolated for all patients with epilepsy, due to various factors such as the metabolic phenotype and the use of enzyme-inducing drugs and inhibitors.

Developmental effects of the protein kinase inhibitor kenpaullone on the sea urchin embryo.

The selection and validation of bioactive compounds require multiple approaches, including in-depth analyses of their biological activity in a whole-animal context. We exploited the sea urchin embryo in a rapid, medium-scale range screening to test the effects of the small synthetic kinase inhibitor kenpaullone. We show that sea urchin embryos specifically respond to this molecule depending on both dose and timing of administration. Phenotypic effects of kenpaullone are not immediately visible, since this molecule affects neither the fertilization nor the spatial arrangement of blastomeres at early developmental stages. Nevertheless, kenpaullone exposure from the beginning of embryogenesis profoundly perturbs specification, detachment from the epithelium, and migration of the primary mesenchyme cells, thus affecting the whole embryonic epithelial mesenchymal transition process. Our results reaffirm the sea urchin embryo as an excellent and sensitive in vivo system, which provides straightforward and rapid response to external stimuli.

A sea urchin in vivo model to evaluate Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is an evolutionarily conserved cellular program, which is a prerequisite for the metastatic cascade in carcinoma progression. Here, we evaluate the EMT process using the sea urchin Paracentrotus lividus embryo. In sea urchin embryos, the earliest EMT event is related to the acquisition of a mesenchymal phenotype by the spiculogenetic primary mesenchyme cells (PMCs) and their migration into the blastocoel. We investigated the effect of inhibiting the epidermal growth factor (EGF) signaling pathway on this process, and we observed that mesenchyme cell differentiation was blocked. In order to extend and validate our studies, we investigated the migratory capability and the level of potential epidermal growth factor receptor (EGFr) targets in a breast cancer cell line after EGF modulation. Altogether, our data highlight the sensitivity of the sea urchin embryo to anti-EMT drugs and pinpoint the sea urchin embryo as a valuable in vivo model system for studying EMT and the screening of anti-EMT candidates.

Valoración terapéutica del agua de mar en modelos experimentales como terapia complementaria en anemia / Valuation therapeutic seawater in experimental models as complementary therapy in anaemia

Introducción: la anemia es un problema de salud pública a nivel mundial, según la Organización Mundial de la Salud afecta en todo el mundo a 1620 millones de personas. En América Latina y el Caribe el 31% de la población presenta problemas de anemia asociadas a dietas deficientes de hierro y relacionadas con malnutrición. Objetivo: evaluar los efectos terapéuticos del agua de mar isotónica microfiltrada al frío como terapia complementaria en modelos biológicos con anemia inducida experimentalmente por dietas pobres en proteínas, vitaminas y minerales, y por medicamentos. Materiales y métodos: se contó durante ocho semanas con 50 ratones cepas NMRI, de ambos géneros y en edad adulto-joven. Se dividieron en cuatro grupos experimentales de 10 ratones cada uno, incluyendo un grupo control. Fueron evaluados al inicio y final del experimento los parámetros hematológicos, pH salival, cobre y zinc. Al final del experimento fueron sacrificados por dislocación cervical y autopsiados para examinar bazo, hígado y riñón. Resultados: los modelos experimentales bajo ingesta de agua de mar con relación al grupo sin agua de mar, independiente del tipo de anemia inducida, evidenciaron diferencias estadísticamente significativas (p< 0,05) con restablecimiento de los parámetros hematológicos. El bazo se observó en tamaño y condiciones normales evidenciando restablecimiento del daño inmunológico ocasionado. Órganos como riñón e hígado no mostraron daños morfológicos. Conclusiones: el agua de mar isotónica resultó útil como terapia complementaria en los modelos experimentales, en casos de anemias causadas por dietas pobres en proteínas, vitaminas y minerales, y desencadenadas por medicamentos. MÉD.UIS. 2014;27(3):9-18.

Introduction: the anaemia is a major public health worldwide, according to the World Health Organization worldwide affects 1620 million people in Latin America and the Caribbean 31% of the population has problems anemia's associated with deficient diets iron and related malnutrition. Objective: evaluating those therapeutic effects of isotonic seawater microfiltered to cold as complementary therapy in biological models with experimentally induced anaemia by poor diets in protein, vitamins and minerals, and by medicaments. Materials and Methods: they counted for eight weeks with 50 NMRI mice of both genders, adult - young age. Were divided into four experimental groups of 10 mice each, including a control group. Evaluated to the beginning and end of the experiment were the hematological parameters, salivary pH, copper and zinc. At the end of the experiment they were sacrificed by cervical dislocation and autopsied stops examine spleen, liver and kidney. Results: the experimental models under seawater intake relative to the group without sea water, independent of the type of induced anaemia, showed statistically significant differences (p < 0.05) with restoration of hematological parameters. The spleen was observed in size and showing restoration of normal immune damage caused. Organs such as kidney and liver showed no morphological damage. Conclusions: isotonic seawater useful as complementary therapy in experimental models, in cases of anemia caused by diets low in protein, vitamins and minerals, and triggered by medicament. MÉD. UIS. 2014;27(3):9-18.

A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.

Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.

Valoración de los efectos fisiológicos y neuroquímicos de altas concentraciones de tetrahidrocannabinol en modelos biológicos / Assessment physiological and neurochemical effects of high concentrations of tetrahydrocannabinol in biological models

El objetivo de esta investigación fue evaluar los efectos fisiológicos y neuroquímicos en 60 ratones machos cepas Naval Medical Research Institute (NMRI) en edad adulto-joven con pesos promedios de 25,45 ± 3,05 g, sometidos durante seis semanas a dosis del principio psicoactivo de la marihuana el Δ-9-tetrahidrocannabinol en concentraciones entre 4 - 20%. Se realizaron tomas de sangre retroorbital para evaluar parámetros hematológicos y bioquímicos antes, durante y post experiencia. Se monitorearon medidas tales como: peso, ingesta de agua, alimentos, actividad locomotora horizontal y vertical, entre otros. Al final de la experiencia se realizo autopsia y toma de muestras de regiones cerebrales, para medir niveles de neurotransmisores aminoacidicos y dopamina. Estos resultados permiten concluir que altas concentraciones del principio psicoactivo de la marihuana hacen más dependiente al consumidor con los consecuentes daños fisiológicos y neurológicos. Esto lleva a que cada vez se necesite más droga para producir el mismo efecto.

The objective of this research was to evaluate the physiological and neurochemical effects in 60 (Naval Medical Research Institute) NMRI male mice strains in young adult - age average weight 25.45 ± 3.05 g, underwent six weeks at doses of the psychoactive ingredient in marijuana the Δ -9-tetrahydrocannabinol in concentrations between 4-20 %. Retroorbital blood shots were conducted to evaluate hematological and biochemical parameters before, during and post experience. Weight, water intake, food, horizontal and vertical locomotors activity include: measures such as monitored. At the end of the experience autopsy was conducted and sampling of brain regions to measure levels of amino acid neurotransmitters and dopamine. These results suggest that high concentrations of the psychoactive ingredient in marijuana consumers become more dependent with consequent physiological and neurological damage. This leads to more and more drugs is needed to produce the same effect.

rs2072135, a low-penetrance variant for chronic lymphocytic leukaemia?

Recent multi-stage genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non-coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P-values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped rs2072135 (GWAS P-value = 0·0024, eQTL P-value = 1·510(-19)) in five independent case-control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined P-value = 1 × 10(-4)), rs2072135 defines a promising risk locus for CLL. Incorporating eQTL information offers an attractive strategy for selecting SNPs from GWAS for validation.

Identification and characterization of PlAlix, the Alix homologue from the Mediterranean sea urchin Paracentrotus lividus.

The sea urchin provides a relatively simple and tractable system for analyzing the early stages of embryo development. Here, we use the sea urchin species, Paracentrotus lividus, to investigate the role of Alix in key stages of embryogenesis, namely the egg fertilization and the first cleavage division. Alix is a multifunctional protein involved in different cellular processes including endocytic membrane trafficking, filamentous (F)-actin remodeling, and cytokinesis. Alix homologues have been identified in different metazoans; in these organisms, Alix is involved in oogenesis and in determination/differentiation events during embryo development. Herein, we describe the identification of the sea urchin homologue of Alix, PlAlix. The deduced amino acid sequence shows that Alix is highly conserved in sea urchins. Accordingly, we detect the PlAlix protein cross-reacting with monoclonal Alix antibodies in extracts from P. lividus, at different developmental stages. Focusing on the role of PlAlix during early embryogenesis we found that PlAlix is a maternal protein that is expressed at increasingly higher levels from fertilization to the 2-cell stage embryo. In sea urchin eggs, PlAlix localizes throughout the cytoplasm with a punctuated pattern and, soon after fertilization, accumulates in larger puncta in the cytosol, and in microvilli-like protrusions. Together our data show that PlAlix is structurally conserved from sea urchin to mammals and may open new lines of inquiry into the role of Alix during the early stages of embryo development.

Actividad antibacteriana del Schinus molle l cultivado en Italia / Antibacterial activity of Schinus molle I grown in Italy

El objetivo de esta investigación fue determinar la actividad antibacteriana del extracto etanolico de las hojas y el extracto hexanoico obtenido de los frutos del Schinus molle L. (Anacardiaceae), cultivado en Italia, con un rendimiento de 32,42 % y 5,63 %, respectivamente. Independientemente del tipo de extracto y de la parte de la planta utilizada, el Schinus molle L., mostró una buena actividad antibacteriana contra bacterias Gram positivas (S. aureus ATCC 29213 y E. faecalis ATCC 29212) con una CMI 16 µg/mL. El rango de CBM de estas bacterias estuvo entre 32 y 64 mg/mL, respectivamente.

The aim of this research was to determine antibacterial activity of etanolic extract of the leaves and hexanoic extract obtained from fruits of Schinus molle L. (Anacardiaceae), grown in Italia. with a yield of 32,42 % and 5,63 %, respectively. Whatever type of extract and the plant part used, Schinus molle L., showed good antibacterial activity against Gram positive bacteria (S. aureus ATCC 29213 and E. faecalis ATCC 29212) with MIC 16 mg/mL. Range of MBC of these bacteria were between 32 and 64 mg/mL respectively.

Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.

Anemias sideroblásticas y puenteado basófilo: Indicador biológico por exposición ocupacional al plomo y sus derivados / Sideroblastic anemia and basophilic bridged: Biological indicator of occupational exposure to lead and its derivatives

En el presente estudio se evaluaron 34 individuos de ambos géneros (n = 15 mujeres y n = 19 hombres) con edades promedios de 37,35 ± 10,37. De los cuales 09 trabajadores de talleres mecánicos y 25 de imprentas gráficas con exposición laboral entre 8 a 10 horas/día. Bajo su consentimiento se les tomo muestra de sangre del antebrazo derecho para evaluar hematológica y morfológicamente glóbulos rojos (punteado basófilo), glóbulos blancos (segmentados neutrofilos), plaquetas y determinar por espectroscopia de absorción atómica con atomización elec trotérmica niveles séricos de plomo. Los resultados analíticos obtenidos para niveles de plomo globales expresados en μgL-1 de 36,03 ± 23,02 evidenciaron correlación directa y positiva con los parámetros bioquímicos evaluados. Ma yo res concentraciones de plomo en sangre coincidieron con pun teados basófilos toscos y alteraciones cualitativas morfológicas tales como hipocromía moderada en glóbulos rojos, granulaciones tóxicas e hipersegmentación en segmentados neutrofilos. No se observaron diferencias estadísticamente significativas con un p = 0,002 entre los grupos expuestos y tiempo de exposición por jornada laboral, más si entre los géneros con un p = 0,087, siendo más evidente el impacto de la exposición ocupacional en hombres, asumiendo mayor masa corporal y por ende mayor densidad ósea por donde este metal tóxico tiene un 95% de afinidad, además de contar el género masculino con mayor producción hematopoyética (La cantidad considerada normal fluctúa entre 4.500.000 (en la mujer) y 5.000.000 (en el hombre) por milímetro cúbico (o microlitro) de sangre). Los resultados obtenidos constituyen una herramienta útil para un pre-diagnóstico a exposición o intoxicación por plomo cuando por infraestructura no se cuente en laboratorios bioanalíticos con un equipo de espectroscopia de ab sorción atómica con atomización electrotérmica.

This study assessed 34 individuals of both genre (n = 15 women and n = 19 men) aged averages of 37.35 ± 10.37. Of whom 09 workers of garages and 25 printing graphs with occupational exposure between 8 to 10 hours per day. Under their consent took them right forearm blood sample to evaluate haematological and morphologically (stippling Basophilic) red blood cells, white blood cells (segmented neutrophils), pla te lets and by Atomic Spectrometry atomization absorption spectroscopy to determine serum levels of lead. The analytical re sults for overall lead levels ex pressed in μgL-1 36.03 ± 23.02 demonstrate positive and direct correlation with the biochemical parameters evaluated. High concentrations of lead in blood coincided with various crude basophiles and qualitative morphological alterations such as hypochromia moderate red globules, toxic granulation’s and hypersegmentation in segmented neutrophils. There were no statistically significant differences with p = 0.002 among exposed groups and exposure time by working day, more if genre with a p = 0.087, being most evi dent impact of occupational exposure in men, assuming greater mass body and therefore greater bone density where this toxic metal has a 95% of affinity’s well as the masculine gender with greater production hematopoietic (considered normal amount fluctuates between 4.500.000 (in women) and 5.000.000 (in humans) per cubic millimeter (microliter) of blood). The results constitute a useful tool for an prediag nostic to exposure or poisoning by lead when infrastructure don’t count in laboratories bioanalytic’s with a team of atomic absorption spectroscopy with spectrometry atomization.

Comprehensive evaluation of the impact of 14 genetic variants on colorectal cancer phenotype and risk.

To comprehensively evaluate the impact of recently identified colorectal cancer (CRC) variants at 1q41, 3q26.2, 8q23.3, 8q24.21, 10p14, 11q23.1, 12q13.13, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12.3, and 20q13.33 on risk and CRC phenotype, the authors analyzed 8,878 cases and 6,051 controls from the United Kingdom ascertained in 1999-2007. The impact of variants on the familial CRC risk was enumerated from age-, sex-, and calendar-specific CRC rates in the 50,924 first-degree relatives of cases. Each of the 14 susceptibility loci independently influences CRC with the risk increasing with increasing number of risk alleles carried (per allele odds ratio = 1.13; P = 2.99 × 10(-58)) and, for those within the upper quintile, there is a 2.3-fold increased risk. In first-degree relatives of cases with ≤17, 18-21, and ≥22 risk alleles, standardized incidence ratios were 1.76, 2.08, and 2.25, respectively. Although the discriminatory attributes of the 14 CRC susceptibility loci for individual risk prediction are poor (area under the curve = 0.58), they may allow subgroups of the population at different CRC risks to be distinguished.

Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial.

BACKGROUND: There is variability in the outcome of patients with chronic lymphocytic leukemia with apparently the same stage of disease. Identifying genetic variants that influence patients' outcome and response to treatment may provide important insights into the biology of the disease. DESIGN AND METHODS: We investigated the possibility that genetic variation influences outcome by conducting a genome-wide analysis of 346,831 single nucleotide polymorphisms in 356 patients entered into a phase III trial comparing the efficacy of fludarabine, chlorambucil, and fludarabine with cyclophosphamide as first-line treatment. Genotypes were linked to individual patients' outcome data and response to chemotherapy. The association between genotype and progression-free survival was assessed by Cox regression analysis adjusting for treatment and clinicopathology. RESULTS: The strongest associations were shown for rs1949733 (ACOX3; P=8.22x10-7), rs1342899 (P=7.72×10(-7)) and rs11158493 (PPP2R5E; P=8.50×10(-7)). In addition, the 52 single nucleotide polymorphisms associated at P<10(-4) included rs438034 (CENPF; P=4.86×10(-6)), previously correlated with cancer progression, and rs2255235 (B2M; P=3.10×10(-5)) and rs2064501 (IL22RA2; P=4.81×10(-5)) which map to B-cell genes. CONCLUSIONS: Our findings provide evidence that genetic variation is a determinant of progression-free survival of patients with chronic lymphocytic leukemia. Specific associations warrant further analyses.

Common genetic variation at 15q25.2 impacts on chronic lymphocytic leukaemia risk.

A genome-wide association study of chronic lymphocytic leukaemia (CLL) suggested that common variants at 15q25.2 (rs783540) and 18q21.1 (rs1036935) influence CLL. To validate these associations and explore their relationship with CLL risk we genotyped case-control datasets from Poland, UK and Italy totalling 1428 cases and 1920 controls. Combined data from these and previously genotyped series (2503 cases and 5789 controls) provided evidence for an association between 15q25.2 and 18q21.1 loci and CLL risk (P(combined) = 1·10 × 10(-7) and 1·30 × 10(-5) respectively). These data provide further evidence for the involvement of common genetic variants in CLL risk and insight into the biological basis of disease development.

Chromosome 7p11.2 (EGFR) variation influences glioma risk.

While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case-control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, P(c) = 7.72 × 10(-8) and 2.09 × 10(-8), respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.

Bioactive indicators related to bioelements of eight unifloral honeys / Indicadores de bioactividad relacionados con bioelementos de ocho mieles uniflorales

Honey is the most popular bee product used by man, with nutritional and medicinal purposes. Its great diversity is attributed to numerous factors (bee type, visited flora, environment, and management). The quality of honey is controlled with routine parameters (free acidity, diastase activity, reducing sugars, ash, water, hydroxymethyfurfural, and sucrose contents). Besides the biochemical quality control, a functional profile is also important for pharmacological applications. In this work, bioactive indicators such as the antioxidant activity, flavonoid and polyphenol contents were evaluated by spectrophotometry, and correlated to the content of six bioelements (Ca, Cu, Fe, Mg, Mn, Zn) measured by atomic absorption spectroscopy, tandem FI-FAAS, in 14 unifloral Czech honeys. The antioxidant activity was 43.13 ± 53.72 mmoles TEAC/100 g honey. The flavonoid content was 5.18 ± 4.19 mg QE/100 g, and the polyphenol content was 45.38 ± 27.20 mg GAE/100 g. Buckwheat honey showed the highest values for these indicators of bioactivity, the acacia honeys the lowest, and the rest of the honeys were comprised between both of them. Honey content of bioelements was 138.19 ± 55.57 ppm Ca (min 77.11 - max 261.65), 0.33 ± 0.41 ppm Cu (min 0.00 - max 1.37), 2.95 ± 1.10 ppm Fe (min 1.34 - max 5.36), 35.08 ± 29.59 ppm Mg (min 8.76 - 128.06), 4.93 ± 3.99 ppm Mn (min 0.34 - max 11.31), 1.07 ± 0.56 ppm Zn (min 0.49 - max 2.52). The antioxidant activity of honey was significantly correlated to its content of cupper, iron, magnesium, manganese and zinc, but was not correlated to calcium.

La miel de abejas es el producto apícola más popular utilizado por el hombre, con fines nutricionales y medicinales. Su gran diversidad se atribuye a numerosos factores (tipo de abeja, flora visitada, ambiente, y manejo). La calidad de la miel se controla con parámetros de rutina: acidez libre, actividad de la diastasa, azúcares reductores, cenizas, humedad, hidroximetilfurfural, sacarosa aparente. Junto con el control de calidad bioquímica, también es importante su perfil funcional para aplicaciones farmacológicas. En este trabajo se evaluaron indicadores de bioactividad como la actividad antioxidante, el contenido de flavonoides y de polifenoles por espectrofotometría, y se correlacionaron con el contenido de seis bioelementos (Ca, Cu, Fe, Mg, Mn, Zn) determinados por espectroscopía de absorción atómica, IF acoplada a EAA con llama, en 14 mieles uniflorales checas. La actividad antioxidante fue 43.13 ± 53.72 mmoles TEAC/100 g miel. El contenido de flavonoides fue 5.18 ± 4.19 mg EQ/100 g, y el de polifenoles fue 45.38 ± 27.20 mg EAG/100 g. La miel de trigo sarraceno mostró los mayores valores en estos indicadores de bioactividad, las mieles de acacia los más bajos, y en el resto de las mieles estuvieron comprendidos entre ambos. El contenido de bioelementos en la miel fue 138.19 ± 55.57 ppm Ca (min 77.11 - max 261.65), 0.33 ± 0.41 ppm Cu (min 0.00 - max 1.37), 2.95 ± 1.10 ppm Fe (min 1.34 - max 5.36), 35.08 ± 29.59 ppm Mg (min 8.76 - 128.06), 4.93 ± 3.99 ppm Mn (min 0.34 - max 11.31), 1.07 ± 0.56 ppm Zn (min 0.49 - max 2.52). La actividad antioxidante de la miel se correlacionó significativamente con su contenido de cobre, hierro, magnesio, manganeso y zinc, pero no se correlacionó con el contenido de calcio.

Estudio de niveles séricos de cobre y zinc y su posible rol como indicadores de dismenorrea primaria / Study of serum levels of copper and zinc and its possible roll like indicators of primary dysmenorrheal

En este trabajo se ha determinado el contenido de cobre y zinc en suero sanguíneo de 39 mujeres con edades comprendidas entre 17 y 21 años de edad, n = 25 con dismenorrea primaria diagnosticada clínicamente y n = 14 grupo control con diagnóstico negativo para la patología estudia-da. Las muestras de suero sanguíneo se obtuvieron antes (a) y durante (d) la menstruación. Fueron analizadas por Espectroscopia de Absorción Atómica con inyección en flujo continuo (EAA-IFC). Las concentraciones obtenidas fueron de 1,56 ± 0,43 mgL-1 de cobre y 1,28 ± 0,34 mgL-1 de zinc antes de la menstruación y 1,06 ± 0,23 mgL-1 de co bre y 1,21 ±0,4 mgL-1 de zinc durante la menstruación, para el grupo control y 1,64 ± 0,52 mgL-1 de cobre y 1,88 ± 0,61 mgL-1 de zinc antes de la menstruación y 1,21 ± 0,34 mgL-1 de cobre y 0,94 ± 0,27 mgL-1 de zinc durante la mens ruaciónt en el grupo estudio. Los elementos determinados en ambos grupos antes del periodo menstrual, no observaron diferencias significativas con p= 0,63 y 0,16 para cobre y zinc, respectivamente. Sin embargo, durante la menstruación, fue evidente una diferencia con p < 0,005. Este resultado nos hace presumir, que el aumento brusco de los niveles séricos de cobre se deba probablemente por la alteración de las prostaglandinas, siendo este bioelemento uno de los responsables de las molestias que se presentan en esta patología y otros efectos secundarios motivados por el descenso brusco del zinc. La relación cobre/zinc se calculo en ambos grupos, con valores de 1,47 y 1,06 antes y durante, respectivamente para el grupo control y para el grupo bajo estudio 1,36 y 1,97 antes y durante, respectivamente.

In this work has determined the copper content and zinc in sanguineous serum of women with primary dysmenorrheal diagnosed clinically and a group of women control with I diagnose negative for the studied pathology. The samples of sanguineous serum taken before (a) and during (d) the second day of the menstruation come from 39 women in ages between 17 and 21 years of age, n = 14 controls and n = 25 women with primary dysmenorrheal. They were processed by Spectroscopy of Atomic Absorption with injection in con-tinuous flow (EAA-IFC). The concentrations obtained of 1.56± 0.43 mgL-1 of copper and 1.28± 0.34 mgL-1 of zinc before menstruation and 1.06 ±0.23 mgL-1 of copper and 1.21 ±0.4 mgL-1 of zinc during the menstruation (second day), for the group control and 1.64 ±0.52 mgL-1 of copper and 1.88 ±0.61 mgL-1 of zinc before menstruation and 1.21± 0.34 mgL-1 of copper and 0.94± 0.27 mgL-1 of zinc during the menstruation in the group study. In relation to the serum levels it initiates to them in both groups were not significant differences (p = 0.63). The zinc, observe he himself behavior, between both groups before the menstruation was not observed significant differences with p = 0.16, nevertheless, during the menstruation I throw p = 0.0033. This result evi-dence that indeed the copper is affected by the alteration of the prostaglandins, being probably one of the people in charge of the annoyances that appear in this pa hologyt and other indirect effect motivated by the abrupt reduction of the zinc, such as alteration in the synthesis and excretion of the hormone stimulating follicle (FSH), of the luteinizante hormone (LH), abnormal development of the ovary, alterations of the menstrual cycle. The copper/zinc re ationl I calculate both groups, with values of 1.47 and 1,06 before and during res pectively for the group control and the group under study 1,36 and 1.97 before and during respectively.