Estudio de los valores de referencia de óxido nítrico alveolar y bronquial en aire exhalado

La inflamación y el remodelado bronquial desempeñan un papel fundamental en la patógena del asma, existiendo evidencia suficiente para considerar que el control de la inflamación contribuye a la evolución de la enfermedad. Es por ello que en los últimos años se ha intensificado la búsqueda de biomarcadores que nos aporten información importante y precisa sobre el proceso inflamatorio en la vía aérea y puedan ser útiles en el manejo de la enfermedad. De entre todos ellos, cabe destacar el ONe dada su sencillez, reproducibilidad y carácter no invasivo, requiriendo menos experiencia que el recuento celular en el esputo y siendo menos costoso que otros métodos analizados. Actualmente se considera un biomarcador del proceso en el asma dada la evidencia científica que demuestra su correlación con la eosinofilia que existe en la vía aérea, evaluada tanto por el esputo inducido como por muestras del lavado broncooalveolar o titulares. Actualmente su técnica se encuentra estandarizada hecho que ha permitido su implementación en la practica clínica habitual. Además las guías internacionales han establecido indicaciones par su uso y los puntos de corte para su interpretación. Sin embargo, menor es la evidencia disponible en torno al modelo bicompartimental y los parámetros que lo definen. El cálculo del J’awNO y la Calv,NO, supone un paso más en el estudio del asma y la categorización de la enfermedad, sin embargo la información disponible sobre su uso en el asma es todavía muy escasa. Teniendo en cuenta las controversias sobre la utilidad del ON como biomarcador en el asma, y la falta de evidencia en torno al papel de sus componentes alveolar y bronquial en el manejo de la enfermedad, el presente trabajo se diseñó con la intención de definir valores de normalidad para Calv,NO y J’awNO en población sana y evaluar su comportamiento en relación con los parámetros demográficas, clínicos, funcionales, el grado de control o lacalidad de vida en el asma

Gamma passing rates of daily EPID transit images correlate to PTV coverage for breast cancer IMRT treatment plans

The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivodosimetry. The transit images acquired during each fraction can be comparedwith a predicted image, if available, or with a baseline image, usually theobtained in the first fraction.This work aims to study the dosimetric impact of thefailing fractions and to evaluate the appropriateness of using a baseline imagein breast plans.Material and methods:Twenty breast patients treated in a Halcyon were ret-rospectively selected. For each patient and fraction, the treatment plan wascalculated over the daily CBCT image.For each fraction,the differences respectto the treatment plan values of OARs and PTV dosimetric parameters wereanalyzed:¿Dmean,¿D95%,¿D98%,¿D2%,¿V36Gy,¿V38.5Gy, and¿V43.5Gy.Daily fractions were ranked according to the differences found in the dosimet-ric parameters between the treatment plan and the daily CBCT to establish thebest fraction.The daily transit images acquired in every fraction were comparedto the first fraction using the global gamma index with the Portal Dosime-try tool. The comparison was repeated using the best fraction image as abaseline.We assessed the correlation of the dosimetric differences obtained from theCBCT images-based treatment plans with the gamma index passing ratesobtained using first fraction and best fraction as baseline.Results:Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%]for the¿PTVD98% and¿PTVD95% per every 10% decrease in the passingrate were found, respectively.When using the best fraction as baseline patients were detected with failingfractions that were not detected with the first fraction as baseline.Conclusion:The gamma passing rates of daily transit images correlate withthe coverage loss parameters in breast IMRT plans. Using first fraction imageas baseline can lead to the non-detectability of failing fractionsPeer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Ecological effects of ionic liquids on microbial activity of a soil and on tree seed germination

The 19th International Electronic Conference on Synthetic Organic Chemistry session Ionic LiquidsIonic liquids (ILs) are considered one of the most promising green alternatives to molecular organic solvents. Nevertheless, before a widespread use of these compounds in a determined application, the knowledge of their ecotoxicity and biodegradability must be defined. In this work the effect of addition of different doses of 1-butil-2,3-dimethylimidazolium trifluoromethanesulfonate, [C4C1C1Im][OTf], on microbial activity of a soil under Pinus pinaster Aiton and on the seed germination of species of P. pinaster , Pinus sylvestris L., Pinus radiata D. Don and Eucalyptus globulus Labill were analyzed. Additionally, seed germination test were also applied to this IL after being subjected to heat treatment. A microcalorimeter Thermal Activity Monitor (TAM-III) TA-Instruments was used to determine the influence of the addition of four doses (10 %, 25 %, 50 % and 75 %) on the microbial activity of a Galician soil, under P. pinaster. Methodology was widely exposed in previous works [1]. From the data obtained in these experiments, the calculation of microbial growth was performed [2]. Seed germination test of selected species were carried out for several doses of ILs (10 %, 1 %, 0.1 % and 0.01 %). The degradation treatment of the IL was carried out during 24 h in an oven at the temperature of 200 °C. Five replies with 25 seeds per Petri dish were incubated in a Phytotron (Climas AGP890) for every species and treatments. Seeds were maintained for 16 h under light at 24 °C and in the dark for 8 h at 16 °C during 45 days, when the germination was completed in all the species [3, 4]. Results of soil microbial activity and germination obtained for this IL were compared with the corresponding to other ILs, previously studied in our laboratory. Dose of 10 % inhibited totally the germination of the four species and dose of 1 % provoked an important reduction with regard to the control, both, for degraded and no-degraded IL. Nevertheless, in spite of all the doses showed differences on calorimetric parameters with regard to control; only the dose of 75 % does not show soil microbial response

Multimodality imaging fusion to guide stereotactic radioablation for refractory complex ventricular tachycardia

Hypertrophic cardiomyopathy; Multimodality imaging; Stereotactic radioablationMiocardiopatía hipertrófica; Imágenes multimodales; Radioablación estereotácticaMiocardiopatia hipertròfica; Imatges multimodals; Radioablació estereotàctic

El ensayo argumentativo como herramienta para el desarrollo del pensamiento crítico en los estudiantes de secundaria

El objetivo de la presente investigación es analizar la enseñanza y aprendizaje del ensayo argumentativo como herramienta para el desarrollo del pensamiento crítico en los estudiantes de secundaria, considerando la importancia que tiene la lectura y escritura de este tipo de texto, para el desarrollo de habilidades mentales importantes en este nivel de educación. Se destaca que el ensayo argumentativo, además de ser un texto que cumple con diversas características lingüístico textuales, es una herramienta que tiene a mano el docente para promover en el educando el desarrollo del pensamiento crítico, dado que favorece la activación de una serie de procesos mentales: analizar, evaluar, comparar, discernir, fundamentar y confrontar puntos de vista. Además, el hecho de escribir, implica también el de leer, indagar, seleccionar, ordenar y procesar la información. También, al escribir este tipo de texto como cualquier otro, se debe tomar conciencia de las actividades cognitivas de la composición escrita que son la planificación, la textualización, la revisión y la corrección del escrito, dentro de las cuales confluyen una serie de estrategias que permiten el logro de un mejor escrito, en el caso del presente trabajo, un mejor ensayo argumentativo. Se destaca también el papel mediador del docente al momento de realizar la tarea de escritura, puesto que el ensayo argumentativo presenta gran complejidad en los estudiantes, por tanto, la orientación permanente y adecuada del docente cuando estos escriben es clave para lograr los propósitos, en materia de enseñanza y aprendizaje de la escritura de este tipo de textos

LPAC syndrome associated with deletion of the full exon 4 in a ABCB4 genetic mutation in a patient with hepatitis C

El síndrome LPAC (low-phospholipid-associated cholelithiasis syndrome) está asociado a mutaciones del gen ABCB4, que codifica la proteína MDR3, esencial en la secreción de fosfatidilcolina en las sales biliares. Este síndrome se caracteriza por una mayor prevalencia en mujeres, síntomas biliares en adultos jóvenes y excelente respuesta al ácido ursodesoxicólico (AUDC). Presentamos el caso de un hombre de 48 años con hepatitis C, genotipo 1b, fibrosis F3, nula respuesta Peg-IFN-α-2b/ribavirina y cólicos nefríticos de repetición. En 2011 desarrolló ictericia, prurito y dolor cólico epigástrico acompañado de aumento sérico de AST, ALT, GGT, bilirrubina y alfafetoproteína, y carga viral (14.600.000 UI/ml). La endoscopia oral, la ecoendoscopia, la angio-TAC y la ecografía-doppler evidenciaron hepatopatía crónica no cirrótica. El cuadro se autolimitó y un año después sufrió un episodio similar. Iniciamos tratamiento con AUDC, con excelente respuesta clínica. El estudio inmunohistoquímico y la secuenciación completa del gen ABCB4 no mostraron alteraciones. La técnica MLPA® detectó deleción heterocigota del exón 4 completo y confirmó la sospecha de síndrome LPAC.Low-phospholipid-associated cholelithiasis syndrome (LPAC) is associated with ABCB4 genetic mutation. ABCB4 encodes MDR3 protein, involved in biliary phosphatidylcholine excretion. Higher prevalence in women, biliary symptoms in young adults and ursodesoxycholic acid (UDCA) response are the main features. We report the case of a 48-year-old man with hepatitis C, genotype 1b, fibrosis F3, null responder to Peg-IFNα2b/ribavirin and nephritic colic. In 2011 he developed jaundice, pruritus and epigastric pain. He showed increased serum levels of AST, ALT, GGT, bilirubin and alpha-fetoprotein, and viral load (14,600,000IU/mL). Pancreatic CT, endoscopic ultrasonography and echo-Doppler showed non cirrhotic chronic liver disease. The episode resolved spontaneously and one year later he suffered a similar episode. UDCA was started with excellent response. An immunohistochemistry study and sequencing of ABCB4 did not find alteration. MLPA® technique detected heterozygous deletion of the full exon 4 confirming LPAC syndrome diagnosis

CD9 controls integrin α5β1-mediated cell adhesion by modulating its association with the metalloproteinase ADAM17

Integrin α5β1 is a crucial adhesion molecule that mediates the adherence of many cell types to the extracellular matrix through recognition of its classic ligand fibronectin as well as to other cells through binding to an alternative counter-receptor, the metalloproteinase ADAM17/TACE. Interactions between integrin α5β1 and ADAM17 may take place both in trans (between molecules expressed on different cells) or in cis (between molecules expressed on the same cell) configurations. It has been recently reported that the cis association between α5β1 and ADAM17 keeps both molecules inactive, whereas their dissociation results in activation of their adhesive and metalloproteinase activities. Here we show that the tetraspanin CD9 negatively regulates integrin α5β1-mediated cell adhesion by enhancing the cis interaction of this integrin with ADAM17 on the cell surface. Additionally we show that, similarly to CD9, the monoclonal antibody 2A10 directed to the disintegrin domain of ADAM17 specifically inhibits integrin α5β1-mediated cell adhesion to its ligands fibronectin and ADAM17.This work has been supported by the grant SAF2016-77096-R from Ministerio Español de Economía y Competitividad (MINECO) awarded to CC, by a grant from Fundación Ramón Areces Ayudas a la Investigación en Ciencias de la Vida y de la Materia, 2014 awarded to MY-M, and by the Deutsche Forschungsgemeinschaft (SFB 877, A6, Z3 and SPP1710) to JG and I

Sex differences in placental protein expression and efficiency in a rat model of fetal programming induced by maternal undernutrition

Fetal undernutrition programs cardiometabolic diseases, with higher susceptibility in males. The mechanisms implicated are not fully understood and may be related to sex differences in placental adaptation. To evaluate this hypothesis, we investigated placental oxidative balance, vascularization, glucocorticoid barrier, and fetal growth in rats exposed to 50% global nutrient re-striction from gestation day 11 (MUN, n = 8) and controls (n = 8). At gestation day 20 (G20), we analyzed maternal, placental, and fetal weights; oxidative damage, antioxidants, corticosterone, and PlGF (placental growth factor, spectrophotometry); and VEGF (vascular endothelial growth factor), 11β-HSD2, p22phox, XO, SOD1, SOD2, SOD3, catalase, and UCP2 expression (Western blot). Compared with controls, MUN dams exhibited lower weight and plasma proteins and higher corticosterone and catalase without oxidative damage. Control male fetuses were larger than female fetuses. MUN males had higher plasma corticosterone and were smaller than control males, but had similar weight than MUN females. MUN male placenta showed higher XO and lower 11β-HSD2, VEGF, SOD2, catalase, UCP2, and feto-placental ratio than controls. MUN females had similar feto-placental ratio and plasma corticosterone than controls. Female placenta expressed lower XO, 11β-HSD2, and SOD3; similar VEGF, SOD1, SOD2, and UCP2; and higher catalase than controls, being 11β-HSD2 and VEGF higher compared to MUN males. Male placenta has worse adaptation to un-dernutrition with lower efficiency, associated with oxidative disbalance and reduced vasculariza-tion and glucocorticoid barrier. Glucocorticoids and low nutrients may both contribute to programming in MUN malesThis research was funded by the Ministerio de Ciencia, Innovación y Universidades (Spain), grant number RTI2018-097504-B-I00, cofinanced with FEDER funds and by the Faculty of Medicine, Khon Kaen University (Thailand), grant number KKU:0514.7.I.12-194

Dibenzo[1,2,5]thiadiazepines are non-competitive GABAA receptor antagonists

"A new process for obtaining dibenzo[c,f][1,2,5]thiadiazepines (DBTDs) and their effects on GABAA receptors of guinea pig myenteric neurons are described. Synthesis of DBTD derivatives began with two commercial aromatic compounds. An azide group was obtained after two sequential reactions, and the central ring was closed via a nitrene to obtain the tricyclic sulfonamides (DBTDs). Whole-cell recordings showed that DBTDs application did not affect the holding current but inhibited the currents induced by GABA (IGABA), which are mediated by GABAA receptors. These DBTDs effects reached their maximum 3 min after application and were: (i) reversible, (ii) concentration-dependent (with a rank order of potency of 2c = 2d > 2b), (iii) mediated by a non-competitive antagonism, and (iv) only observed when applied extracellularly. Picrotoxin (which binds in the channel mouth) and DBTDs effects were not modified when both substances were simultaneous applied. Our results indicate that DBTD acted on the extracellular domain of GABAA channels but independent of the picrotoxin, benzodiazepine, and GABA binding sites. DBTDs used here could be the initial model for synthesizing new GABAA receptor inhibitors with a potential to be used as antidotes for positive modulators of these receptors or to induce experimental epilepsy.