Analytical method development for ultra-trace determination of human pharmaceuticals in aqueous samples. Assessing the performance of a sewage treatment plant

Research focus in environmental pollution has recently been extended from more classical environmental pollutants such as PCBs or pesticides to pharmaceuticals and steroid hormones, which are designed to be biologically active and enter the environment primarily through regular domestic use. Consequently, it is important to monitor these substances concentrations in the effluents of sewage treatment plants (STPs) and in the environment in order to evaluate their associated risks. Moreover, the study of the occurrence and fate of these compounds within the STP would aid in improving their removal. Therefore, in this thesis the occurrence of seven pharmaceuticals (ibuprofen, naproxen, diclofenac, fluoxetine, ofloxacin, norfloxacin, ciprofloxacin), two metabolites (norfloxacin, clofibric acid), one toxic degradation product (4-isobutylacetophenone) and three steroid hormones (ethinylestradiol, estradiol, estrone) and their removal rates were investigated in a tertiary STP in the south of Sweden. Perspectives on sample preparation for the analysis of pharmaceuticals and steroid hormones in wastewater are presented. In this thesis, special attention is devoted toward the development of various sample preparation methodologies preceding the final separation and detection systems, liquid or gas chromatography coupled to DAD or MS. Solid-phase extraction (SPE) is widely used to extract polar compounds such as pharmaceuticals and personal care products (PPCPs). Different SPE sorbents were compared showing that hydrophilic-lipophilic balance (HLB) polymer has a higher trapping capacity than ion-exchange sorbents, but lacks high selectivity leading to large matrix effects in LC-ESI-MS/MS. Furthermore a molecularly imprinted polymer (MIP) based SPE was developed for non-steroidal antiinflamaroty drugs (NSAIDs) and clofibric acid extraction from wastewater resulting in no appreciable matrix effect. Membrane-based extraction techniques were as well evaluated for the extraction of steroid hormones, basic drugs and a toxic degradation product of ibuprofen. These methodologies had the advantage of simplicity, low cost and high enrichment factors. Finally these methods were applied to study the occurrence and removal rates of the target analytes at Kristianstad´s STP. Results showed that removal rates were above 90%, except for diclofenac, clofibric acid, estrone and ofloxacin. For the first time 4-isobutylacetophenone (4-IBAP) has been monitored along a STP. Relatively high concentrations of 4-IBAP were observed in the inlet of the STP, but since good removal rates were obtained during the biological step, as for many other drugs, it was not detected in the effluent

Fármacos y suplementos nutricionales para llevar en el botiquín del alpinista

Cada vez son más los individuos que acuden a montañas de gran altitud, con el riesgo que esta práctica entraña. Por tanto, es de gran importancia conocer los peligros y déficits que esta práctica puede conllevar, con el fin de evitarlos o poderlos tratar. Es por ello que la preparación del botiquín, tanto con fines preventivos como paliativos o curativos tiene una gran transcendencia. Entre los suplementos nutricionales más importantes que debemos llevar están los multivitamínicos minerales, y entre los fármacos destacan aquellos para tratar y prevenir el mal agudo de montaña, destacando acetazolamida

Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.This study was partly supported by the DIOMED project (INTERREG IVB SUDOE 1/P1/E178)

Removal of TiO 2 nanoparticles from water by low pressure pilot plant filtration

Rising use of nanoparticles in manufacturing as well as in commercial products bring issues related to environmental release and human exposure. A large amount of TiO2 nanoparticles will eventually reach wastewater treatment plants. Low pressure membrane filtration has been suggested as a feasible treatment of water streams. This study investigated first at laboratory scale the influence of: i) membrane material, ii) pore size and iii) water chemistry on nTiO2 removal. TiO2 retention was governed by the cake layer formation mechanism and significant retention of nanoparticles was observed even for filters having considerably larger pores than nTiO2. PVDF showed a great potential for nTiO2 rejection. Additionally, filtration pilot plant experiments were carried out using PVDF membranes (0.03 and 0.4 μm pore size). The release of nTiO2 in the pilot scale filtration system was always above the instrumental detection limit (> 1.5 μg/L) and in most cases below 100 μg/L regardless of the pore size and applied conditions. The nTiO2 membrane breakthrough predominantly occurred in the first few minutes after backwashes and ceased when the cake layer was formed. Ultrafiltration and microfiltration were comparable with rejection of nTiO2 above 95% at similar permeate flow rates. Nevertheless, ultrafiltration is more promising than microfiltration because it allowed longer operation times between backwash cycles.This work was funded by the Provincial Government of Bizkaia (6-12-TK-2010-0013)

Lessons Learned from Applying Adaptation Pathways in Heatwave Risk Management in Antwerp and Key Challenges for Further Development

Heat exposure is a well-known health hazard, which causes several problems ranging from thermal discomfort or productivity reduction to the aggravation of existing illnesses and death. Climate projections foresee an increase in the frequency and intensity of heat-related impacts on human health. To reduce these climate risks, governments need a better understanding of not only the scale and the factors affecting those risks, but also how to prepare and protect the city and citizens against these risks and prevent them through effective policy making. Therefore, climate adaptation decisions need to be made in complex systems with manifold uncertainties. In response to these deep uncertainties, different planning approaches have been developed to assist policymakers in decision making. This paper is focused on one of the dynamic adaptive policy planning approaches: the adaptation pathway. This approach allows designing alternative feasible plans that are flexible and can respond when new information appears or when conditions in the environment change. This paper presents a structured methodology for designing adaptation pathways. The work describes a high-level adaptation pathway covering heatwave impacts on productivity and health at city level in Antwerp to ensure the city adapts to future conditions. Lastly, a summary is provided of the lessons learned and the challenges of this approach are discussed.This work was supported by the European Community’s Seventh Framework Programme (grant agreement no. 308497), Project RAMSES “Reconciling Adaptation, Mitigation and Sustainable Development for Cities” (2012–2017). In addition, this study has received partial funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 653522 (RESIN−Climate Resilient Cities and Infrastructures project)

Effect of Microalgae and Macroalgae Extracts on Non-Alcoholic Fatty Liver Disease

The present review aims to gather scientific evidence regarding the beneficial effects of microalgae and macroalgae extracts on non-alcoholic fatty liver disease (NAFLD). The described data show that both microalgae and macroalgae improved this alteration. The majority of the reported studies analysed the preventive effects because algae were administered to animals concurrent with the diet that induced NAFLD. The positive effects were demonstrated using a wide range of doses, from 7.5 to 300 mg/kg body weight/day or from 1 to 10% in the diet, and experimental periods ranged from 3 to 16 weeks. Two important limitations on the scientific knowledge available to date are that very few studies have researched the mechanisms of action underlying the preventive effects of microalgae on NAFLD and that, for the majority of the algae studied, a single paper has been reported. For these reasons, it is not possible to establish the best conditions in order to know the beneficial effects that these algae could bring. In this scenario, further studies are needed. Moreover, the beneficial effects of algae observed in rodent need to be confirmed in humans before we can start considering these products as new tools in the fight against fatty liver disease.This study was funded by University of the Basque Country (grant: GIU18-173) and Carlos III Research Institute (CIBERobn) (grant CB12/03/30007)

Muscle fatigue in athletes: physical, nutritional and pharmacological methods for improving recovery

Antecedentes: Una rápida recuperación en los deportistas es un aspecto fundamental para continuar entrenando a intensidades elevadas y seguir progresando más, especialmente en deportes en los que se compite todos los días. Los ejercicios excéntricos producen rupturas de miofibrillas musculares, sobre todo si se llevan a cabo de forma intensa y no habitual provocando daño muscular. Este daño muscular produce una fatiga muscular que limita el rendimiento muscular, disminuyendo la fuerza, el pico de potencia, o la velocidad. Por ello, es importante conocer de qué medios de recuperación muscular disponen los deportistas. Objetivo: Conocer las causas y consecuencias de la fatiga muscular y hacer una revisión sobre las ayudas ergogénicas: físicas, nutricionales y farmacológicas que existen para una rápida y mejor recuperación muscular y orgánica y poder conocer las más eficaces de una manera integral en la práctica deportiva. Métodos: Revisión bibliográfica en distintas bases de datos tanto en lengua castellana como inglesa, siguiendo 4 estrategias específicas, tratando de ofrecer un estado de conocimiento actual sobre las diferentes estrategias de recuperación post-ejercicio. Resultados: Ciertos deportes, como los de equipo o los que tienen un gran componente excéntrico que conllevan una mayor destrucción muscular, requieren una intervención especial para recuperar los microtraumatismos que se producen durante su práctica (entrenamientos y competición). Hay diferentes formas de mejorar la recuperación, como métodos físicos (masaje deportivo, electroestimulación, contrastes de agua), estrategias nutricionales (hidratación e ingesta de hidratos de carbonos y proteínas), ergonutricionales (aminoácidos ramificados, glutamina, β-hdroximetil butirato, creatina) y farmacológicas (antiinflamatorios, analgésicos, inmunomoduladores farmacológicos). Estas estrategias pueden ser básicas para conseguir una recuperación integral del deportista.Background: It is fundamental in athletes a rapid recovery, it is a really important aspect to continue training at high intensities and also to continue progressing, especially in sports when you compete every day. Eccentric exercises produce muscular myofibril ruptures, especially at high intensities, causing muscle damage. This damage produces muscular fatigue that limits its performance, decreasing the force, the peak power or/and the speed. For that reason, it is important to know the methods to recover from muscle fatigue. Aims: To know the causes and consequences of muscular fatigue and to review the ergogenic aids: physical, nutritional and pharmacological methods for a faster and better recovery. Likewise, to know the most effective recovery methods in sports, in a comprehensive way. Methods: Literature review on different databases both Spanish and English, following 4 specific strategies, trying to offer a current knowledge about different strategies of post-exercise recovery. Results: Some sports, like team sport or those who have a great eccentric component that involve greater muscle destruction; require special intervention to retrieve traumatisms that occur during sport practice (training and competition). There are different ways to improve it such as physical methods (sports massage, electrical stimulation, water contrasts), nutritional strategies (hydration and carbohydrate and protein intake), ergonutritional (branched chain amino acids, glutamine, β-hidroximetil butyrate, creatine) and pharmacological (analgesic, anti-inflammatory, immunomodulatory drug). These strategies can be basic to achieve a full recovery of the athlete

Resveratrol and Pterostilbene, Two Analogue Phenolic Compounds, Affect Aquaglyceroporin Expression in a Different Manner in Adipose Tissue

Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would modify AQPs expression in white and brown adipose tissues from Wistar rats fed an obesogenic diet, and to establish a potential relationship with the delipidating properties of these compounds. Consequently, thirty-six rats were divided into four groups: (a) group fed a standard diet; and three more groups fed a high-fat high-sucrose diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30 mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous white adipose tissues and interscapular brown adipose tissue were dissected. AQPs gene expression (RT-PCR) and protein expression (western-blot) were measured. In white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight and prevented the decrease in AQP9 induced by obesogenic feeding, and thus glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal adipose tissue weight and avoided the decrease in AQPs related to glycerol release induced by high-fat high-sucrose feeding, suggesting the involvement of lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7 seemed not to be involved in the previously reported thermogenic activity of both phenolic compounds.This research has been supported by MINECO (AGL-2015-65719), Instituto de Salud Carlos III (CIBERobn) and Basque Government (IT-572-13; PA18/03)

The influence of dietary conditions in the effects of resveratrol on hepatic steatosis

Non-alcoholic fatty liver disease (NAFLD) is considered the major cause for the development of chronic liver alterations. Hepatic steatosis is the most benign and common form of NAFLD, although its potential to evolve into more detrimental liver alterations makes its treatment necessary. In this regard, much attention has been paid to polyphenols, with resveratrol being one of the most studied ones. This review is aimed at studying the effects induced by resveratrol on hepatic steatosis in both preclinical studies conducted under different feeding conditions (overfeeding, normal feeding and caloric restriction), and in clinical trials. The vast majority of studies have been conducted by administering the polyphenol at the same time as an obesogenic diet. Under these experimental conditions, resveratrol has shown effectiveness improving diet-induced excessive liver lipid accumulation. Data are scarce for studies carried out by administering resveratrol under standard or energy-restricted feeding conditions. In this regard, while resveratrol retains its effectiveness, ameliorating hepatic steatosis under standard feeding conditions, such an effect has not been reported for the administration of the polyphenol under energy restriction. With regard to clinical trials, in the majority of them, resveratrol did not show its effectiveness in improving hepatic steatosis. This lack of effect could be due to significant differences in the experimental procedures (mainly the length of the experimental period). The relevance of liver fat content at the baseline should also be considered. Altogether, there is no sufficient scientific support so far for proposing resveratrol as a tool for hepatic steatosis treatment.This study has been supported by grants from Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional, under grant AGL-2015-65719-R MINECO/FEDER, (UE), Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007 and University of the Basque Country, under Grant GIU18-173