Intoxicación por plomo en un ternero de la zona minera de Sierra Madrona y el Valle de Alcudia

[EN]: We notify the first reported case of lead (Pb) poisoning in a calf from the old mining district of Sierra Madrona and Alcudia Valley (Spain), which appeared in a farm with visible signs of historic mining activity in the surrounding land. The blood Pb level found in this calf was 311 μg/dL, and was associated to several symptoms of clinical Pb poisoning, including severe paralysis, loss of sensitivity from hip to the hind legs and incoordination. Soils, plants and water points inside the farm showed Pb levels above the threshold values to be classified as highly polluted soils, toxic pastures for livestock and non-potable water for humans. This report indicates that Pb pollution denotes a health risk for cattle reared in the mining area of Sierra Madrona and Alcudia Valley.[ES]: Se notifica el primer caso registrado de intoxicación por plomo (Pb) en un ternero del antiguo distrito minero de Sierra Madrona y el Valle de Alcudia (España), que apareció en una finca ganadera con restos visibles de antiguas actividades mineras en los terrenos circundantes. El nivel de Pb en sangre detectado en el animal fue de 311 μg/dL, y estuvo asociado a diversos síntomas de intoxicación clínica por Pb, que incluyen parálisis severa, pérdida de sensibilidad en los cuartos traseros e incoordinación. Los suelos, las plantas y los puntos de agua presentes en la finca mostraron niveles de Pb por encima de los valores umbral, siendo considerados como suelos altamente contaminados, pastos tóxicos para el ganado y agua no potable para el consumo humano. Estos datos indican que la contaminación por Pb implica un riesgo para la salud del ganado criado en la zona minera de Sierra Madrona y el Valle de Alcudia.The Department of Education and Science of the Junta de Comunidades de Castilla-La Mancha funded this study (PCI08-0096-1295).Peer Reviewe

Lead in sheep exposed to minig pollution: implications for animal and public health

Trabajo presentado a la Energy and Environment Knowledge Week, celebrada en Toledo (España) del 20 al 22 de noviembre de 2013.Peer Reviewe

Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05)

PURPOSEThe Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials.METHODSThis single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade >= 3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria.RESULTSForty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).CONCLUSIONAtezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile

Supplemental Information 3: Dataset including repeated measures for the carotenoid-supplement experiment. The dataset excludes birds receiving diquat (see Methods). Description of variables inserted as comments on variable names.

Colorful ornaments have been the focus of sexual selection studies since the work of Darwin. Yellow to red coloration is often produced by carotenoid pigments. Different hypotheses have been formulated to explain the evolution of these traits as signals of individual quality. Many of these hypotheses involve the existence of a signal production cost. The carotenoids necessary for signaling can only be obtained from food. In this line, carotenoid-based signals could reveal an individual's capacity to find sufficient dietary pigments. However, the ingested carotenoids are often yellow and became transformed by the organism to produce pigments of more intense color (red ketocarotenoids). Biotransformation should involve oxidation reactions, although the exact mechanism is poorly known. We tested the hypothesis that carotenoid biotransformation could be costly because a certain level of oxidative stress is required to correctly perform the conversion. The carotenoid-based signals could thus reveal the efficiency of the owner in successfully managing this challenge. In a bird with ketocarotenoid-based ornaments (the red-legged partridge Alectoris rufa), the availability of different carotenoids in the diet (i.e. astaxanthin, zeaxanthin and lutein) and oxidative stress were manipulated. The carotenoid composition was analyzed and quantified in the ornaments, blood, liver and fat. A number of oxidative stress biomarkers were also measured in the same tissues. First, we found that color and pigment levels in the ornaments depended on food levels of those carotenoids used as substrates in biotransformation. Second, we found that birds exposed to mild levels of a free radical generator (diquat) developed redder bills and deposited higher amounts of ketocarotenoids (astaxanthin) in ornaments. Moreover, the same diquat-exposed birds also showed a weaker resistance to hemolysis when their erythrocytes were exposed to free radicals, with females also enduring higher oxidative damage in plasma lipids. Thus, higher color production would be linked to higher oxidative stress, supporting the biotransformation hypothesis. The recent discovery of an avian oxygenase enzyme involved in converting yellow to red carotenoids may support our results. Nonetheless, the effect could also depend on the abundance of specific substrate carotenoids in the diet. Birds fed with proportionally higher levels of zeaxanthin showed the reddest ornaments with the highest astaxanthin concentrations. Moreover, these birds tended to show the strongest diquat-mediated effect. Therefore, in the evolution of carotenoid-based sexual signals, a biotransformation cost derived from maintaining a well-adjusted redox machinery could coexist with a cost linked to carotenoid acquisition and allocation (i.e. a resource allocation trade-off).Esther García-de Blas was supported by a predoctoral grant (JAE-PRE) from the Consejo Superior de Investigaciones Científicas (CSIC) co-financed by Fondo Social Europeo (EU). This study was funded by Consejería de Educación y Ciencia, Junta de Comunidades de Castilla la Mancha (project ref.: PII1I09-0271-5037) and Ministerio de Economía y Competitividad (CGL2009-10883-C02-02 and CGL2015-69338-C2-2-P) from the Spanish Government.Peer Reviewe

Oxidative Stress in Wild Boars Naturally and Experimentally Infected with Mycobacterium bovis

Reactive oxygen and nitrogen species (ROS-RNS) are important defence substances involved in the immune response against pathogens. An excessive increase in ROS-RNS, however, can damage the organism causing oxidative stress (OS). The organism is able to neutralise OS by the production of antioxidant enzymes (AE); hence, tissue damage is the result of an imbalance between oxidant and antioxidant status. Though some work has been carried out in humans, there is a lack of information about the oxidant/antioxidant status in the presence of tuberculosis (TB) in wild reservoirs. In the Mediterranean Basin, wild boar (Sus scrofa) is the main reservoir of TB. Wild boar showing severe TB have an increased risk to Mycobacterium spp. shedding, leading to pathogen spreading and persistence. If OS is greater in these individuals, oxidant/antioxidant balance in TB-affected boars could be used as a biomarker of disease severity. The present work had a two-fold objective: i) to study the effects of bovine TB on different OS biomarkers (namely superoxide dismutase (SOD), catalasa (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and thiobarbituric acid reactive substances (TBARS)) in wild boar experimentally challenged with Mycobacterium bovis, and ii) to explore the role of body weight, sex, population and season in explaining the observed variability of OS indicators in two populations of free-ranging wild boar where TB is common. For the first objective, a partial least squares regression (PLSR) approach was used whereas, recursive partitioning with regression tree models (RTM) were applied for the second. A negative relationship between antioxidant enzymes and bovine TB (the more severe lesions, the lower the concentration of antioxidant biomarkers) was observed in experimentally infected animals. The final PLSR model retained the GPX, SOD and GR biomarkers and showed that 17.6% of the observed variability of antioxidant capacity was significantly correlated with the PLSR X's component represented by both disease status and the age of boars. In the samples from free-ranging wild boar, however, the environmental factors were more relevant to the observed variability of the OS biomarkers than the TB itself. For each OS biomarker, each RTM was defined as a maximum by one node due to the population effect. Along the same lines, the ad hoc tree regression on boars from the population with a higher prevalence of severe TB confirmed that disease status was not the main factor explaining the observed variability in OS biomarkers. It was concluded that oxidative damage caused by TB is significant, but can only be detected in the absence of environmental variation in wild boar

Lead pollution in large game and livestock from the mining area of Alcudia Valley and Sierra Madrona: use of biomarkers for the study of sublethal effects

Memoria presentada por Jaime Rodríguez Estival para optar al grado de doctor por la Universidad de Castilla-La Mancha (Departamento de Ciencia y Tecnología Agroforestal y Génetica) y realizada en el Instituto de Investigación en Recursos Cinegéticos (IREC-CSIC-UCLM-JCCM).La minería es una de las actividades humanas que genera un impacto ambiental más severo, especialmente cuando se centra en la extracción y tratamiento de metales pesados como el plomo (Pb). Los residuos generados en estos procesos mineros pueden contener altos niveles de contaminación en la actualidad, especialmente si las zonas afectadas fueron abandonadas tras siglos de explotación sin ser sometidas a ningún proceso de restauración. En esta tesis se estudia el impacto de la contaminación minera que persiste en el antiguo distrito minero del Valle de Alcudia y Sierra Madrona sobre la fauna cinegética y ganadera que habita la zona, a través de la determinación de efectos subletales mediante el uso de biomarcadores. Los trabajos que componen la tesis muestran que los ciervos (Cervus elaphus) y jabalíes (Sus scrofa) que habitan este distrito minero están expuestos de forma crónica a la contaminación por plomo que todavía persiste en el entorno de las viejas escombreras, minas y fundiciones que se encuentran diseminadas por la zona, siendo la generación de estrés oxidativo uno de los mecanismos por los que el plomo podría ejercer sus efectos tóxicos, principalmente a través de su efecto sobre los componentes del sistema antioxidante. En este sentido, tanto los antioxidantes endógenos (glutatión, superóxido dismutasa y glutatión peroxidasa) como los exógenos (vitaminas A y E) se ven afectados por la exposición a la contaminación por plomo, aunque de forma diferenciada, en el caso de algunos de los antioxidantes estudiados, en cada especie estudiada (ciervo y jabalí), lo que probablemente esté relacionado con la susceptibilidad de cada especie a padecer los efectos de la exposición a la contaminación. Por otro lado, en esta tesis se ha observado que los niveles de exposición al Pb detectados en los ungulados silvestres pueden causar efectos adversos sobre el tejido óseo (concretamente, cambios en la composición mineral de los huesos), que a su vez podrían estar relacionados con el efecto negativo del Pb sobre los niveles hepáticos de vitamina A; y sobre el sistema inmune, a través de la inducción de alteraciones (sobreexpresión) en la expresión genética de ciertas citoquinas, como la interleuquina-4 en el caso del ciervo, y el interferón-gamma en el caso del jabalí. Al igual que los ungulados silvestres, los ungulados domésticos que se crían en las fincas ganaderas ubicadas en el antiguo distrito minero del Valle de Alcudia y Sierra Madrona están expuestos de forma crónica a niveles de plomo que se relacionan con efectos bioquímicos adversos en sangre, representados principalmente por la inhibición de la síntesis del grupo hemo (enzima δ-ALAD). Más del 90% de las vacas y más del 13% de las ovejas expuestas a la contaminación mostraron niveles de plomo en sangre correspondientes con una intoxicación subclínica. Como conclusión, los resultados de esta tesis sugieren que la contaminación minera que persiste en el antiguo distrito minero del Valle de Alcudia y Sierra Madrona podría representar un riesgo para la salud y el medio ambiente aún en la actualidad.Jaime Rodríguez-Estival was supported by a predoctoral grant from the Junta de Comunidades de Castilla-La Mancha, Spain. This study has been funded by the Department of Education and Science of Junta de Comunidades de Castilla- La Mancha with the projects PCC-05-004-2 and PCI08-0096-1295.Peer Reviewe

Small mammals as biosentinels of health effects from exposure to oil and gas related contaminants. An integrated experimental and field based approach

Resumen del trabajo presentado al Society of Environmental Toxicology and Chemistry North America 35th Annual Meeting, celebrado en Vancouver (Canadá) del 9 al 13 de noviembre de 2014.Canada’s oil sands activities, marked by ongoing controversy about environmental impacts, produce complex mixtures of pollutants including polycyclic aromatic hydrocarbons (PAHs) and metals such as lead (Pb), cadmium (Cd) and mercury (Hg) which are potentially deposited onto soil, water and vegetation posing a risk for surrounding ecosystems and wildlife. Recent studies encompassing the Athabasca Oil Sands Region report increased deposition of total PAHs (mainly alkyl-PAHs) and metals in melted snow within 50 km of upgrading facilities, compared to more distant, undisturbed areas, suggesting that these compounds are a consequence of oil sands activities. Here we present results of an integrated experimental and field-based research approach designed to evaluate how PAHs and metals affect the health of local wildlife in northern Alberta, using herbivorous small mammals as sentinel species. Firstly, an experimental study using lab mice (as a surrogate for wild small mammals) was developed to simulate the subchronic exposure to environmentally relevant concentrations of pollutants. Mice were exposed to a mixture of alkyl-PAHs (food), and/or to a mixture of challenge metals (water) during 28 days. Several biomarkers of exposure and/or effect were evaluated in these groups, and compared with those from control mice. Biomarkers included the antibody response to a challenge antigen, thyroid (T3, T4) and reproductive (T and E2) hormones in plasma, and biomarkers of oxidative stress in liver including glutathione (GSH) redox status, malondialdehyde (MDA), and levels of vitamins A (retinyl esters and all-trans retinols) and E (α-tocopherol). The hepatic biotransformation enzyme, 7-ethoxyresorufin-O-deethylase (EROD), a well-studied indicator of contaminant exposure, was also analyzed in liver. Absorbed PAHs and metals were respectively determined in muscle, fat and kidneys to determine bioavailability and measure tissue residues. Based on findings from the experiment study, the most sensitive biomarkers were selected for subsequent field studies to evaluate exposure and health effects in wild small mammals on the oil sands-affected areas in northern Alberta. Two industrial sites (one in the early reclamation stage, and other in mature reclamation) and a reference site were selected for the study on wild small mammals. Highlights from this integrated research approach will be presented.Peer Reviewe

Exposure to anthropogenic chemicals in wild carnivores: a silent conservation threat demanding long-term surveillance

Resumen del trabajo presentado al SETAC (Society of Environmental Toxicology and Chemistry) Europe 30th Annual Meeting: Open Science for Enhanced Global Environmental Protection, celebrado Online del 3 al 7 de mayo de 2020.Peer reviewe

Exposure to anthropogenic chemicals in wild carnivores: a silent conservation threat demanding long-term surveillance

Top predators are fundamental drivers in maintaining ecosystems and preserving biodiversity. However, a number of species have experienced severe population declines and currently face critical conservation challenges. Although exposure to chemical contaminants has been recognized as a meaningful threat for wild carnivores, their population effect has been more rarely assessed. Here, we focus on species in the mammalian order Carnivora to review some of the most relevant case studies that have led to identification of chemical exposure (i.e. organohalogen compounds, mercury, anticoagulant rodenticides, and intentional poisoning) as an anthropogenic force that may compromise the conservation of top predators. We point out the challenges that should be considered in future ecotoxicological research on wild carnivores, highlighting the relevance of long-term monitoring surveillance in conservation programs.JRE was supported by a Research and Innovation Strategy for Smart Specialisation (RIS3) postdoctoral contract (2017/11747) from the Junta de Comunidades de Castilla-La Mancha. This review is a result of CGL2013–40975-R project, from I+D+I National Plan funded by the Spanish Ministry of Economy and Competitiveness.Peer reviewe