SSThe coexistence and diversity of Candidatus methylomirabilis oxyfera-like and anammox bacteria in sediments of an urban eutrophic lake / SLa coexistencia y diversidad de bacterias Candidatus methylomirabilis oxyfera y anammox en sedimentos de un lago urbano eutrófico

Tangxun Lake is the largest urban lake in China, which is polluted by multiple wastewaters, and now is severely eutrophic. We detected diversity, abundance, and the coexistence of Candidatus Methylomirabilis oxyfera-like and anammox bacteria in different horizontal and vertical directions of the lake sediments through qPCR and clone library. Phylogenetic tree analysis showed that the Ca. Methylomirabilis oxyfera-like and anammox bacteria exhibited high diversity, and they belonged to group B—E and Ca. Brocadia genus, respectively. These two bacteria displayed higher diversity in polluted area than in other areas. Furthermore, they had great spatial variation of abundance both horizontally and vertically. The abundance of anammox bacteria was significantly higher than that of Ca. Methylomirabilis oxyfera-like bacteria. The stronger the human interference were, the higher abundances these two bacteria exhibited horizontally, whereas both their abundances and the ratio of anammox to Ca. Methylomirabilis oxyfera-like bacteria decreased with the increasing depth. Redundancy analysis indicated that nitrate was the most influential environmental factor to the abundance of these two bacteria. Ammonia, nitrite, total nitrogen, and organic matters were in positive correlation with the abundance of these two bacteria. Nitrate was slightly negatively correlated with the abundance of Ca. Methylomirabilis oxyfera-like bacteria, while it was positively correlated with that of anammox bacteria. Our results provided an insight into the effects of environmental factors such as ammonia, nitrite, and nitrate on the diversity and abundances of these two bacteria and theoretical basis for restoration of water.(AU)

High serum nitrates levels in non-survivor COVID-19 patients / Altas concentraciones séricas de nitratos en pacientes fallecidos por COVID-19

Objective: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. Design: A prospective observation study was carried out. Setting: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). Patients: COVID-19 patients admitted to the ICU. Interventions: Determination of serum nitrate levels at ICU admission. Main variable of interest: Mortality at 30 days. Results: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006–1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006–1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73–92%; p<0.001), APACHE II (AUC=85%; 95%CI=75–96%; p<0.001) and SOFA (AUC=78%; 95%CI=63–92%; p=0.005) based on the DeLong method. The Kaplan–Meier analysis found patients with serum nitrates levels>68.4μmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3–863.9; p<0.001). Conclusions: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation (AU)

Objetivo: Se han encontrado niveles más elevados de nitratos en la sangre de pacientes con enfermedad del coronavirus 2019 (COVID-19) que en sujetos sanos. Por lo tanto, el objetivo de estudio consistió en explorar la posible asociación entre los niveles séricos de nitratos y la mortalidad de pacientes por COVID-19. Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI. Intervenciones: Se midieron los niveles séricos de nitratos al ingreso en la UCI. Variable de interés principal: Mortalidad a los 30 días. Resultados: Los pacientes fallecidos (n=11) comparados con los supervivientes (n=42) presentaron mayores APACHE-II (p<0,001), SOFA (p=0,004) y niveles séricos de nitratos (p=0,001). Los análisis de regresión logística mostraron una asociación entre los niveles séricos de nitratos al ingreso en la UCI y la mortalidad a los 30 días controlando por SOFA (OR:1.021; IC 95%:1.006-1.036; p=0,01) o APACHE-II (OR:1.023; IC 95%:1.006-1.041; p=0,01). No encontramos diferencias en el área bajo la curva (ABC) para la predicción de mortalidad entre los niveles séricos de nitratos (ABC:83%; IC 95%:73-92%; p<0,001), APACHE-II (ABC:85%; IC 95%:75-96%; p<0,001) y SOFA (ABC:78%; IC 95%:63-92%; p=0,005) con el método de DeLong. El análisis de Kaplan-Meier mostró que los pacientes que tenían niveles séricos de nitratos al ingreso en la UCI>68,4μmol/l presentaban mayor riesgo de fallecer (hazard ratio:138,8; IC 95%:22,3-863,9; p<0,001). Conclusiones: El principal nuevo hallazgo fue la asociación entre los niveles séricos de nitratos y la mortalidad de pacientes COVID-19 controlando por SOFA o APACHE-II; pero estudios de mayor tamaño muestral son necesarios para confirmar este resultado (AU)

Adaptation of granular sludge microbial communities to nitrate, sulfide, and/or p-cresol removal

Effluents from petroleum refineries contain a toxic mixture of sulfide, nitrogen, and phenolic compounds that require adequate treatment for their removal. Biological denitrification processes are a cost-effective option for the treatment of these effluents, but the knowledge on the microbial interactions in simultaneous sulfide and phenol oxidation in denitrifying reactors is still very limited. In this work, microbial community structure and macrostructure of granular biomass were studied in three denitrifying reactors treating a mixture of inorganic (sulfide) and organic (p-cresol) electron donors for their simultaneous removal. The differences in the available substrates resulted in different community assemblies that supported high removal efficiencies, indicating the community adaptation capacity to the fluctuating compositions of industrial effluents. The three reactors were dominated by nitrate reducing and denitrifying bacteria where Thiobacillus spp. were the prevalent denitrifying organisms. The toxicity and lack of adequate substrates caused the endogenous decay of the biomass, leading to release of organic matter that maintained a diverse although not very abundant group of heterotrophs. The endogenous digestion of the granules caused the degradation of its macrostructure, which should be considered to further develop the denitrification process in sulfur-based granular reactors for treatment of industrial wastewater with toxic compounds

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A new family of nitrate/nitrite transporters involved in denitrification

Denitrifying bacteria carry out nitrate and nitrite respiration inside and outside the cell, respectively. In Thermus thermophilus, nitrate and nitrite transport processes are carried out by major facilitator superfamily (MFS) transporters. The sequence of the nar operon of nitrate-only respiring strains of T. thermophilus includes two tandemly organized MFS transporter genes (narK and narT) of the NarK1 and NarK2 families. Both can function as nitrate/nitrite antiporters, but NarK has been proposed as more specific for nitrate whereas NarT more specific for nitrite. In some nitrate- and nitrite-respiring strains of the same species, a single MFS transporter (NarO) belonging to a different MFS subfamily appears. To analyze the role of this single MFS in the same genetic context, we transferred the two types of nar operon to the aerobic strain HB27, and further included in both of them the ability to respire nitrite. The new denitrifying strains HB27dn, with two MFS, and HB27dp, with a single one, were used to isolate mutants devoid of transporters. Through in trans complementation experiments, we demonstrate that the NarO single MFS works efficiently in the transport of both nitrate and nitrite

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Metahemoglobinemia en lactantes mayores de un año / Metahemoglobinemia in infants over one year

Antecedentes y objetivo: La metahemoglobinemia es un cuadro de intoxicación aguda típico de niños menores de un año. Se produce por un exceso de nitratos que producen la oxidación del hierro de la hemoglobina impidiendo su adecuada unión al oxígeno. Es más frecuente en lactantes debido a su inferior actividad enzimática. Pacientes: Dos casos de lactantes de 15 meses con cuadros de metahemoglobinemia tras ingesta de verduras, atípicos por la edad de los pacientes y por la severidad inicial en el primer caso, que llegó a simular un cuadro séptico. En ambos casos se logró la resolución del cuadro con adecuada oxigenoterapia. Conclusiones: Aunque la clínica más frecuente es cianosis asociada a dificultad respiratoria, la metahemoglobinemia puede presentarse con cuadros más severos y confusos y en mayores de un año. El tratamiento de elección es oxigenoterapia a altas concentraciones y azul de metileno como antídoto por vía intravenosa únicamente en casos seleccionados. La ingesta de vegetales es el principal causante de este cuadro, por lo que es importante dar la información adecuada a los padres sobre el consumo y la conservación de estos alimentos

Background and objectives: Methaemoglobinaemia is a typical acute intoxication disorder in children under one year old. It is produced by excess nitrates which induce the haemoglobin's iron oxidation, preventing its adequate binding to oxygen. It is more frequent in infants due to its lower enzymatic activity. Patients: Two cases of 15-month-old infants with methaemoglobinaemia after the intake of vegetables, atypical by the age of the patients and the initial severity in the first case that simulated a septic syndrome. Both cases evolved well with adequate oxygen therapy. Conclusions: Although the most frequent clinical manifestation is cyanosis associated with respiratory distress, methaemoglobinaemia can present with more severe and confusing symptoms. The main treatment is oxygen therapy at high concentrations and methylene blue as an intravenous antidote only in selected cases. The intake of vegetables is the main cause of this in infants, so it is important to give adequate information to parents about the consumption and preservation of these foods during the first year of life

Óxido nítrico: ¿un posible nuevo biomarcador en insuficiencia cardíaca? Relación con hipertensión pulmonar secundaria a insuficiencia cardíaca izquierda / Nitric oxide: A new possible biomarker in heart failure? Relationship with pulmonary hypertension secondary to left heart failure

La insuficiencia cardíaca (IC) es un creciente problema médico por lo que resulta de interés el estudio de nuevos biomarcadores para su mejor caracterización, y en este sentido, evaluamos productos metabólicos (nitritos y nitratos) del óxido nítrico, especies reactivas del oxígeno (ROS), NADPH y superóxido dismutasa (SOD) y su posible valor predictivo en pacientes con IC. Además, estudiamos potenciales diferencias entre pacientes con y sin hipertensión pulmonar secundaria (HPS), considerados de peor pronóstico. En IC, demostramos disminución significativa de los niveles plasmáticos de nitritos y nitratos y SOD, mientras que ROS y NADPH se encontraban incrementados. Estos resultados concuerdan con los cambios fisiopatológicos propios de la IC. También demostramos en pacientes con IC e HPS que los niveles plasmáticos de nitritos y nitratos así como SOD estaban disminuidos respecto a IC sin HPS, mientras que ROS y NADPH estaban aumentados. Por lo tanto, nuestros resultados indican que óxido nítrico, ROS, NADPH y SOD podrían ser considerados como posibles marcadores en IC y además permitirían caracterizar a los pacientes con HPS (AU)

Heart failure (HF) is a growing medical problem and it is of interest to study new biomarkers for better characterisation. In this sense, nitric oxide, reactive oxygen species (ROS), NADPH, and superoxide dismutase (SOD) were evaluated, along with their possible predictive value in patients with HF. An analysis was also performed on the potential differences between patients with and without secondary pulmonary hypertension (SPH), considered to have a worse prognosis. A significant decrease of nitric oxide and SOD was noted in HF, whereas ROS and NADPH were increased. These results agree with the pathophysiological changes characteristic of HF. It was also demonstrated that in patients with HF and SPH that nitric oxide and SOD were decreased when compared to HF without SPH, whereas ROS and NADPH were increased. Therefore, our results suggest that nitric oxide, ROS, NADPH, and SOD, could be considered as possible markers in HF, and could also characterise patients with SPH (AU)

Nuevas evidencias en el manejo de pacientes con insuficiencia cardiaca con fracción de eyección preservada / New evidence for the management of patients with heart failure with preserved ejection fraction

Introducción: Aunque en ocasiones los nitratos se emplean para el alivio de los síntomas en el paciente con insuficiencia cardiaca, realmente no se conocen sus efectos en el paciente con insuficiencia cardiaca y fracción de eyección preservada, a pesar de que algunas series muestran cómo los nitratos son empleados en el 15-50% de estos pacientes. El estudio (Nitrate's Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction (NEAT-HFpEF) comparó el efecto de mononitrato de isosorbida frente a placebo sobre la actividad diaria en pacientes con insuficiencia cardiaca y fracción de eyección preservada. Métodos: Se realizó un ensayo clínico multicéntrico, doble ciego y de diseño cruzado, en el que se incluyó a 110 pacientes ambulatorios con al menos 50 años de edad e insuficiencia cardiaca con una fracción de eyección preservada (≥ 50%) en tratamiento médico estable. Los pacientes fueron aleatorizados a mononitrato de isosorbida, con un régimen de titulación de 6 semanas (de 30mg a 60mg a 120mg una vez al día) o a placebo, con el consiguiente cruce al otro grupo por 6 semanas. La variable primaria del estudio fue el nivel de actividad diaria cuantificada mediante acelerómetro durante la fase de 120mg. Resultados: En comparación con el placebo, los pacientes tratados con 120mg de mononitrato de isosorbida mostraron una tendencia no significativa a presentar una menor actividad diaria (p=0,06) y un descenso significativo en las horas de actividad por día (-0,30 h; p=0,02). Asimismo, la actividad en el grupo de mononitrato de isosorbida durante todas las dosis fue menor que en el grupo placebo. Además, los niveles de actividad disminuyeron significativamente y de manera progresiva conforme aumentaba las dosis de mononitrato de isosorbida. No hubo diferencias significativas entre los grupos ni en el test de los 6 min, ni en la calidad de vida, ni en los niveles de péptidos natriuréticos. Numéricamente hubo más discontinuaciones en los pacientes con tratamiento activo, así como más efectos adversos. Conclusiones: La adición de mononitrato de isosorbida al tratamiento con insuficiencia cardiaca y fracción de eyección preservada se tradujo en una menor actividad diaria. Además, tampoco mejoró la calidad de vida de estos pacientes (AU)

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Muerte súbita recuperada en un consumidor de cocaína / Aborted sudden death in a cocaine consumer

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Influencia del tratamiento con nitratos intravenosos en la mortalidad precoz de pacientes con insuficiencia cardiaca aguda. Estudio NITRO-EAHFE / Influence of intravenous nitrate treatment on early mortality among patients with acute heart failure. NITRO-EAHFE Study

Introducción y objetivos. La evidencia sobre la influencia pronóstica de los nitratos intravenosos en pacientes con insuficiencia cardiaca aguda es escasa. El objetivo del estudio es determinar la influencia de este tratamiento en mortalidad precoz y reconsulta. Métodos. Estudio de cohortes, multicéntrico, prospectivo de pacientes con insuficiencia cardiaca aguda en servicios de urgencias en 2 periodos (mayo de 2009 y noviembre-diciembre de 2011). Se incluyó pacientes con presión arterial sistólica > 110 mmHg agrupados en función de si recibieron nitroglicerina intravenosa o no. Las variables objetivo fueron mortalidad a 3, 7, 14 y 30 días y reconsulta a 30 días. Para determinar la influencia pronóstica del tratamiento se realizó un propensity score mediante regresión logística. Resultados. De 4.897 individuos se incluyeron 3.178. Fallecieron a 30 días 308 (9,7%) y reconsultaron 465 (17%). La edad media era de 79,5 ± 10,0 años y 796 (25%) recibieron nitratos intravenosos. Tras emparejarlos quedaron 685 individuos en cada grupo. La hazard ratio de los nitratos para mortalidad a 30 días fue 1,21 (intervalo de confianza del 95%, 0,87-1,70) y para reconsulta 0,93 (intervalo de confianza del 95%, 0,71-1,22). Los resultados fueron similares para la mortalidad a 3, 7 y 14 días (hazard ratio = 1,05 [intervalo de confianza del 95%, 0,56-1,96], hazard ratio = 1,20 [intervalo de confianza del 95%, 0,74-1,94] y hazard ratio = 1,23 [intervalo de confianza del 95%, 0,82-1,84], respectivamente). En presencia de edema de pulmón hipertensivo, el grupo de nitratos mostró una hazard ratio de 0,88 (intervalo de confianza del 95%, 0,47-1,63) para mortalidad a 30 días. Conclusiones. Los nitratos intravenosos no influyen en mortalidad precoz ni en reconsulta en pacientes con insuficiencia cardiaca aguda (AU)

Introduction and objectives. There is little evidence on the prognostic influence of intravenous nitrates in patients with acute heart failure. Our purpose was to determine the influence of this treatment on early mortality and new visits. Methods. Prospective, multicenter cohort study of patients with acute heart failure in an emergency room during 2 periods (May 2009 and November-December 2011). Patients with systolic blood pressure > 110 mmHg were included, grouped according to whether they received intravenous nitroglycerin or not. Endpoints were mortality at 3, 7, 14, and 30 days and new visits at 30 days. The propensity score was estimated by logistic regression to determine the prognostic influence of the treatment. Results. We included 3178 of 4897 individuals. A total of 308 (9.7%) had died within 30 days and 465 (17%) attended new visits. The mean (standard deviation) age was 79.5 (10.0) years, and 796 (25%) patients received intravenous nitrates. After matching, there were 685 individuals in each group. The hazard ratio for 30-day mortality with nitrates was 1.21 (95% confidence interval, 0.87-1.70) and was 0.93 for new visits (95% confidence interval, 0.71-1.22). The results were similar for mortality at 3, 7, and 14 days (hazard ratio = 1.05 [95% confidence interval, 0.56-1.96], hazard ratio = 1.20 [95% confidence interval, 0.74-1.94], and hazard ratio = 1.23 [95% confidence interval, 0.82-1.84], respectively). In the presence of hypertensive pulmonary edema, the nitrates group showed a hazard ratio of 0.88 (95% confidence interval, 0.47-1.63) for 30-day mortality. Conclusions. Intravenous nitrates do not influence early mortality or new visits in patients with acute heart failure (AU)

Contenido en nitratos de aguas de consumo público españolas / Nitrate concentrations in tap water in Spain

Objetivo: Analizar el contenido en nitratos de aguas de consumo público de una muestra de ciudades españolas. Material y métodos: Se determinaron los nitratos por cromatografía iónica en aguas de consumo público recogidas entre enero y abril de 2012 en 108 municipios españoles de más de 50.000 habitantes, donde viven 21.290.707 personas. El número total de muestras analizadas fue de 324. Resultados: La concentración mediana de nitratos es 3,47mg/l (rango: 0,38-66,76; rango intercuartílico: 4,51). El agua del 94% de los municipios estudiados contiene menos de 15mg/l. Solo en tres municipios la concentración es de más de 25mg/l y en uno es superior a 50mg/l. Conclusiones: El nivel de nitratos de la mayoría de las aguas de consumo público que abastecen los municipios donde habita casi la mitad de la población española tiene niveles inferiores a 15mg/l (AU)

Objective: To determine nitrate concentrations in drinking water in a sample of Spanish cities. Material and methods: We used ion chromatography to analyze the nitrate concentrations of public drinking water in 108 Spanish municipalities with more than 50,000 inhabitants (supplying 21,290,707 potential individuals). The samples were collected between January and April 2012. The total number of samples tested was 324. Results: The median nitrate concentration was 3.47mg/L (range: 0.38-66.76; interquartile range: 4.51). The water from 94% of the municipalities contained less than 15mg/L. The concentration was higher than 25mg/L in only 3 municipalities and was greater than 50mg/L in one. Conclusions: Nitrate levels in most public drinking water supplies in municipalities inhabited by almost half of the Spanish population are below 15mg/L (AU)

La insuficiencia cardiaca aguda en España: certezas e incertidumbres / Acute heart failure in Spain: certainties and uncertainties

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Ingesta dietética de nitratos en bebés y niños españoles y riesgo de metahemoglobinemia / Dietary intake of nitrate in Spanish infants and children and risk of methemoglobinemia

Pese a que el consumo de verduras y hortalizas es recomendable tanto en adultos como en bebés y niños pequeños, existe el riesgo de que estos últimos ingieran a través de dichos alimentos cantidades elevadas de nitratos que incrementen el riesgo de padecer metahemoglobinemia. Aunque la ingesta media de nitratos en la población infantil europea no supera los márgenes de seguridad, un análisis llevado a cabo por la Autoridad Europea de Seguridad Alimentaria (EFSA) en 2010 reveló que el consumo de espinacas puede estar implicado en ciertos casos de metahemoglobinemia infantil. La Agencia Española de Seguridad Alimentaria y Nutrición (AESAN) consideró en 2011 que las acelgas, debido a su notable consumo en España, también pueden suponer un riesgo para la población infantil si su ingesta es elevada. A las recomendaciones de la AESAN, que es conveniente que conozca cualquier profesional sanitario del ámbito de la nutrición infantil, resulta prudente añadir que un elevado consumo de borraja (Borago officinalis, una hortaliza muy consumida en Navarra, La Rioja y Aragón en la elaboración de purés hechos en casa) también puede estar implicado en la metahemoglobinemia infantil. En cualquier caso, tal y como señalan tanto la EFSA como la AESAN, cuando se comparan los riesgos/beneficios de la exposición de nitratos por el consumo de verduras y hortalizas, prevalecen los efectos beneficiosos de su consumo (AU)

Although the consumption of vegetables is recommended for adults, infants and young children, there is a risk that their consumption results in a high intake of nitrates that increases the risk of methemoglobinemia. Even though the average nitrate intake in children does not exceed the European safety threshold, an analysis conducted by the European Food Safety Authority (EFSA) in 2010 revealed that the consumption of spinach may be involved in certain cases of infant methemoglobinemia. The Spanish Agency for Food Safety and Nutrition (AESAN) found in 2011 that chards, because of its remarkable consumption in Spain, may also pose a risk for children. In addition to the AESAN recommendations, that any health care professional in the field of infant nutrition should know, it is prudent to add that a high consumption of borage (Borago officinalis, a vegetable widely consumed in Navarra, La Rioja and Aragón in homemade purees) may also be involved in infant methemoglobinemia. In any case, and as EFSA and AESAN point out, the benefits of eating vegetables prevail over the risks of the exposure to nitrates linked to their consumption (AU)

Effect of nitrate and L-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats

Reduced nitric oxide availability and a heterogeneous pattern of nitric oxide synthase activity in some tissues have been reported in hypothyroidism. This study aimed at determining the effects of oral nitrate and L-arginine administration on serum, heart, and aorta nitric oxide metabolite concentrations in fetal hypothyroid rats. In an experimental study, pregnant Wistar rats were administrated tap water or 0.02 % of 6-propyl-2-thiouracil in drinking water during pregnancy and their male pups were followed (n = 8/group). In adult progeny, serum, heart, and aorta nitric oxide metabolite concentrations were measured by the Griess method after 1-week administration of sodium nitrate (500 mg/L) or L-arginine (2 %) in drinking water. Serum thyroid hormone and thyroid-stimulating hormone levels were also measured. Compared to controls, fetal hypothyroid progeny had significantly lower nitric oxide metabolite concentrations in heart (0.32 ± 0.07 vs. 0.90 ± 0.14 nmol/mg protein, p = 0.004) and aorta (2.98±0.56 vs. 6.15±0.74 nmol/mg protein, p = 0.011) tissues. Nitrate therapy restored heart nitric oxide metabolite levels decreased by fetal hypothyroidism, while L-arginine administration further decreased aorta nitric oxide metabolite levels. Sodium nitrate increased and L-arginine decreased serum nitric oxide metabolite levels in both control and fetal hypothyroid animals. In conclusion, nitrate therapy restores decreased heart nitric oxide metabolite levels, whereas L-arginine decreases aorta nitric oxide metabolite levels even further in fetal hypothyroid rats, findings relevant to the cardiovascular consequences of congenital hypothyroidism in adulthood (AU)

Nitrate and trace elements in municipal and bottled water in Spain / Nitrato y elementos traza en agua embotellada y municipal en España

Objectives: To describe levels of nitrate and trace elements in drinking water from the study areas of a multicase-control study of cancer in Spain (MCC-Spain). Methods: A total of 227 tap water samples were randomly collected from 67 municipalities in 11 provinces and the nine most frequently consumed bottled water brands were sampled to measure levels of nitrate, arsenic, nickel, chromium, cadmium, lead, selenium and zinc. Results: The median nitrate level was 4.2mg/l (range<1-29.0), with similar levels in rural and urban municipalities (p=0.86). Trace elements were unquantifiable in 94% of tap water samples. Differences between areas were significant for nitrate (p<0.001) and arsenic (p=0.03). Only nitrate was quantifiable in bottled water (range 2.3-15.6mg/l). Conclusions: Nitrate levels in municipal water differed between regions and were below the regulatory limit in all samples, including bottled water. Trace element levels were low and mainly unquantifiable in tap and bottled water (AU)

Objetivos: Determinar las concentraciones de nitrato y de elementos traza en el agua de consumo de las áreas del estudio Multicaso-Control de Cáncer en España (MCC-Spain). Métodos: Se tomaron al azar 227 muestras de agua municipal en 67 municipios de 11 provincias, y 9 muestras de las aguas embotelladas más consumidas, para cuantificar la cantidad presente de nitrato, arsénico, níquel, cromo, cadmio, plomo y zinc. Resultados: La mediana de las cifras de nitrato fue 4,2mg/l (rango<1-29,0), con similares resultados en municipios urbanos y rurales (p=0,86). Los elementos traza fueron incuantificables en el 94% de las muestras de agua municipal. Se observaron diferencias entre áreas para nitrato (p<0,001) y arsénico (p=0,03). Solo el nitrato fue cuantificable en el agua embotellada (rango 2,3-15,6mg/l). Conclusiones: La cantidad de nitrato en el agua municipal difiere entre regiones y es menor que el límite regulatorio en todas las muestras. Los elementos traza son mayormente incuantificables tanto en el agua municipal como en la embotellada (AU)

Markers of Airway Inflammation in the Exhaled Breath Condensate of Preschool Wheezers

Antecedentes: Los leucotrienos (LT), isoprostanos y nitritos/nitratos, que son biomarcadores de la inflamación de las vías aéreas, y el estrés oxidativo, pueden ser detectados en el condensado del aire exhalado (CAE). El objetivo de este estudio fue evaluar el LTB4, LTE4, 8-isoprostano, nitritos y nitratos en el CAE de niños preescolares sanos y con sibilancias. Material y métodos: Se realizó un estudio transversal en el que se incluyeron 21 niños sanos no atópicos y 25 pacientes con sibilancias recurrentes. El LTB4, LTE4 y 8-isoprostano, se midieron en el CAE mediante enzimoinmunoensayo, y los nitritos/nitratos mediante método colorimétrico. Resultados: Las concentraciones de LTB4 fueron mayores en los niños con episodios de sibilancias que en controles sanos (76 pg/ml vs 20 pg/ml, p<0,001); El LTE4 se incrementó también en niños con episodios de sibilancias en comparación con niños sanos (68 pg/ml vs 35 pg/ml, p<0,001). Las concentraciones de nitritos fueron mayores en los niños con episodios de sibilancias que en los controles (14 pg/ml vs 9,7 pg/ml, p<0,03). No hubo diferencias en las concentraciones de 8-isoprostano y nitratos entre el grupo de niños enfermos y el grupo control. Conclusiones: Nuestros hallazgos sugieren que el CAE es un método no invasivo para la evaluación de la inflamación de las vías respiratorias y del estrés oxidativo en lactantes y niños en edad preescolar. Las concentraciones de LTB4, LTE4 y de nitritos, se incrementaron en niños con episodios recurrentes de sibilancias en comparación con los controles sanos (AU)

Background: Leukotrienes (LT), isoprostanes, and nitrites/nitrates are biomarkers of airway inflammation and oxidative stress that can be detected in exhaled breath condensate (EBC). The aim of this study was to evaluate LTB4, LTE4, 8-isoprostane, and nitrite/nitrate levels in the EBC of healthy and wheezing preschool children. Methods: We included 21 healthy nonatopic children and 25 patients with recurrent wheezing episodes in a cross-sectional study. LTB4, LTE4, and 8-isoprostane concentrations were measured directly in EBC using a specific enzyme immunoassay; nitrite/nitrate concentrations were measured using a colorimetric assay. Results: LTB4 concentrations were higher in children with wheezing episodes than in healthy controls (76 pg/mL vs 20 pg/mL, P<.001). LTE4 was increased in children with wheezing episodes than in healthy controls (68 pg/mL vs 35 pg/mL, P<.001). Nitrite concentrations were higher in children with wheezing episodes than in healthy controls (14 pg/mL vs 9.7 pg/mL, P<.03). We found no differences in 8-isoprostane and nitrate concentrations between the patients and the healthy controls. Conclusions: Our findings suggest that EBC is a suitable noninvasive method for the assessment of airway inflammation and oxidative stress in preschool children. Levels of LTB4, LTE4, and nitrites were higher in children with recurrent wheezing episodes than in healthy controls (AU)

Role of the denitrifying Haloarchaea in the treatment of nitrite-brines

Haloferax mediterranei is a denitrifying halophilic archaeon able to reduce nitrate and nitrite under oxic and anoxic conditions. In the presence of oxygen, nitrate and nitrite are used as nitrogen sources for growth. Under oxygen scarcity, this haloarchaeon uses both ions as electron acceptors via a denitrification pathway. In the present work, the maximal nitrite concentration tolerated by this organism was determined by studying the growth of H. mediterranei in minimal medium containing 30, 40 and 50 mM nitrite as sole nitrogen source and under initial oxic conditions at 42 °C. The results showed the ability of H. mediterranei to withstand nitrite concentrations up to 50 mM. At the beginning of the incubation, nitrate was detected in the medium, probably due to the spontaneous oxidation of nitrite under the initial oxic conditions. The complete removal of nitrite and nitrate was accomplished in most of the tested conditions, except in culture medium containing 50 mM nitrite, suggesting that this concentration compromised the denitrification capacity of the cells. Nitrite and nitrate reductases activities were analyzed at different growth stages of H. mediterranei. In all cases, the activities of the respiratory enzymes were higher than their assimilative counterparts; this was especially the case for NirK. The denitrifying and possibly detoxifying role of this enzyme might explain the high nitrite tolerance of H. mediterranei. This archaeon was also able to remove 60 % of the nitrate and 75 % of the nitrite initially present in brine samples collected from a wastewater treatment facility. These results suggest that H. mediterranei, and probably other halophilic denitrifying Archaea, are suitable candidates for the bioremediation of brines with high nitrite and nitrate concentrations (AU)

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Control by Fur of the nitrate respiration regulators NarP and NarL in Salmonella enterica

Anaerobic metabolism is controlled by several transcriptional regulators, including ArcA, Fnr, NarP, and NarL, with the Fnr and ArcA proteins sensitive to the cell's redox status. Specifically, the two-component ArcAB system is activated in response to the oxidation state of membrane-bound quinones, which are the central electron carriers of respiration. Fnr, by contrast, directly senses cellular oxidation status through the [4Fe-4S] cluster present in its own structure. In this study, a third additional redox-associated pathway that controls the nitrate respiration regulators NarL and NarP was identified. The results showed that, in Salmonella enterica, the expression of these two transcriptional regulators is under the control of Fur, a metalloregulator that senses the presence of Fe2+ and regulates the homeostasis of this cation inside the cell. Thus, the Fur- Fe2+ complex increases the expression of narL and represses that of narP. Furthermore, studies of S. enteric mutants defective in the Fur-regulated sRNA RfrA and RfrB showed that those sRNA control both narP and narL expression. These results confirm Fur as a global regulator based on its involvement not only in iron uptake and detoxification but also in the control of nitrate/nitrite respiration by sensing cellular redox status (AU)

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Utilidades terapéuticas de la ranolazina en la cardiopatía isquémica / Therapeutic value of ranolazine in ischemic heart disease

La angina crónica estable afecta en torno al 6,7% de las mujeres y el 5,7% de los varones; además, la angina estable supone cerca de un tercio de las formas de cardiopatía isquémica y es uno de los síntomas que más limita la calidad de vida. La ranolazina proporciona una nueva estrategia antianginosa que ejerce su principales acciones previniendo la sobrecarga patológica de sodio y calcio intracelulares desencadenadas por la isquemia miocárdica; como consecuencia, no afecta a la frecuencia cardiaca y la presión arterial ni facilita la aparición de arritmias. La ranolazina aumenta el tiempo de ejercicio hasta la aparición de angina y disminuye el número de crisis de angina y la necesidad de tratamiento con nitratos. El único ensayo clínico realizado en el síndrome coronario agudo sin elevación del ST mostró una reducción significativa en la isquemia recurrente y tendencia a disminuir la mortalidad. Por último, la ranolazina es bien tolerada y no produce efectos secundarios graves ni taquicardias ventriculares (AU)

Chronic stable angina affects 6.7% of women and 5.7% of men. In addition, the condition predominates in one-third of all forms of ischemic heart disease and is one of the symptoms that can have the greatest impact on quality of life. Ranolazine provides a new form of antianginal therapy whose principle effect is to prevent the pathological intracellular sodium and calcium overload that results from myocardial ischemia. Consequently, the drug does not affect the heart rate or blood pressure, or induce arrhythmias. Ranolazine increases the duration of physical activity achievable before the onset of angina and decreases both the number of angina attacks and the need for nitrates. The only clinical trial of ranolazine performed in patients with non-ST elevation acute coronary syndrome demonstrated a significant reduction in recurrent ischemia and a trend towards lower mortality. Lastly, ranolazine is well tolerated, has no serious side effects, and does not induce ventricular tachycardia (AU)

Melatonin and oxidative stress

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Assessment of the addition of Thiobacillus denitrificans and Thiomicrospira denitrificans to chemolithoautotrophic denitrifying bioreactors

The aim of the present study was to assess the impact of adding cultures of Thiobacillus denitrificans and Thiomicrospira denitrificans to two upflow anaerobic sludge bed (UASB) reactors: one inoculated with granular sludge and the other filled only with activated carbon (AC). The performances of the bioreactors and the changes in biomass were compared with a non-bioaugmented control UASB reactor inoculated with granular sludge. The reactors inoculated with granular sludge achieved efficiencies close to 90% in nitrate and thiosulfate removal for loading rates as high as 107 mmol-NO3 -/l per day and 68 mmol-S2O3 2-/l per day. Bioaugmentation with Tb. denitrificans and Tm. denitrificans did not enhance the efficiency compared to that achieved with non-bioaugmented granular sludge. The loading rates and efficiencies were 30-40% lower in the AC reactor. In all the reactors tested, Tb. denitrificans became the predominant species. The results strongly suggest that this bacterium was responsible for denitrification and sulfoxidation within the reactors. We additionally observed that granules partially lost their integrity during operation under chemolithoautotrophic conditions, suggesting limitations for long-term operation if bioaugmentation is applied in practice (AU)

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